Age-related Macular Degeneration

Die vorliegende Übersetzung des Leitfadens zum »Humphrey Field
Analyzer« beruht auf der von der Firma Allergan Humphrey herausgegebenen zweiten Auflage des »FieldAnalyzer Primer« aus dem Jahre 1987. In neueren Softwarefreigaben Sind einige Formulierungen überarbeitet worden, so daß sie nicht mehr mit denen älterer deutscher Bedienungsanleitungen identisch sind. So entspricht z.B. in diesem Leitfaden der Begriff »Standard«-Strategie dem früheren »Beginnhelligkeitautomatisch«.
Die zur Erläuterung im englischen Original gewählten Fallbeispiele
wurden beibehalten. Die Abbildungen, die die Ausdrucke des »Field Analyzers« zeigen, sind in ihrer englischen Form übernommen worden, die Bildunterschriften wurden aber ins Deutsche übersetzt. Bei den im deutschen Sprachraum ausgelieferten Geräten der Firma Allergan Humphrey erscheinen nicht nur auf den Bildschirmen der Perimeter, sondern auch auf den Ausdrucken die Begriffe in deutscher Sprache. Im Anhang sind deshalb einige Muster der deutschsprachigen Ausdrucke
wiedergegeben. Zusammen mit den entsprechenden Abschnitten in den deutschsprachigen Bedienungsanleitungen sollte es stets möglich sein, ein hier auf Englisch wiedergegebenes Bild eines Perimetrieergebnisses richtig zu interpretieren. Dabei ist es sehr hilfreich, daß die Anordnung der Begriffe auf den Ausdrucken im Deutschen wie im Englischen völlig übereinstimmt. Man findet also die gewünschten Ergebnisse in beiden Sprachen jeweils an der gleichen Stelle auf dem Ausdruck.

• ARHL is characterized by increasing age and hearing loss from low to high frequencies. • Factors involved in ARHL are divided into two genetic and nongenetic categories. • Inflammation, apoptosis, and oxidative stress are three main mechanisms of ARHL. Age-related hearing loss (ARHL) is a type of bilateral hearing loss that progresses from low frequencies to high frequencies with age. This disorder is classified as a multifactorial disease. Factors involved in ARHL pathology are divided into two categories of genetic and non-genetic factors. The genes involved in this disorder include three categories of genes involved in cochlear structure and function, genes correlated with oxidative stress, and mitochondrial-dependent genes. Oxidative stress, apoptosis, and inflammation are the three main causes of ARHL. Damage to hair cells induces intrinsic and extrinsic apoptosis and can therefore accelerate ARHL. Some process in cells leads to the production of high amounts of reactive oxygen species including hydrogen peroxide (H 2 O 2), anion superoxide (O 2-), and hydroxyl radical (OH). Reactive oxygen species or ROS can generally have several sources including nitric oxide synthase, NADPH oxidase, microsomal, mitochondrial, and proxisomal pathways. In typical conditions, ROS is produced and neutralized by antioxidant enzymes such as superoxide dismutase, catalase, and glutathione, balancing cell homeostasis. Though, the process of aging, drug treatment, and some other factors upset this homeostasis, and this causes oxidative stress and induction of ARHL in the cells of the auditory system. The aim of this study was to describe the cellular and molecular mechanisms involved in ARHL with a focus on oxidative stress.

Wound healing is one of the most complex biological processes to occur in life. Repair of tissue following injury involves dynamic interactions between multiple cell types, growth factors, inflammatory mediators and components of the extracellular matrix (ECM). Aberrant and uncontrolled wound healing leads to a non-functional mass of fibrotic tissue. In the eye, fibrotic disease disrupts the normally transparent ocular tissues resulting in irreversible loss of vision. A common feature in fibrotic eye disease is the transdifferentiation of cells into myofibroblasts that can occur through a process known as epithelial-mesenchymal transition (EMT). Myofibroblasts rapidly produce excessive amounts of ECM and exert tractional forces across the ECM, resulting in the distortion of tissue architecture. Transforming growth factor-beta (TGFβ) plays a major role in myofibroblast transdifferentiation and has been implicated in numerous fibrotic eye diseases including corneal opacification, pterygium, anterior subcapsular cataract, posterior capsular opacification, proliferative vitreoretinopathy, fibrovascular membrane formation associated with proliferative diabetic retinopathy, submacular fibrosis, glaucoma and orbital fibrosis. This review serves to introduce the pathological functions of the myofibroblast in fibrotic eye disease. We also highlight recent developments in elucidating the multiple signaling pathways involved in fibrogenesis that may be exploited in the development of novel anti-fibrotic therapies to reduce ocular morbidity due to scarring.

This work reviews concepts regarding oxidative stress and the mechanisms by which endogenous and exogenous factors produce reactive oxygen species (ROS). It also surveys the relationships between oxidative stress, circadian rhythms, and retinal damage in humans, particularly those related to light and photodamage. In the first section, the production of ROS by different cell organelles and biomolecules and the antioxidant mechanisms that antagonize this damage are reviewed. The second section includes a brief review of circadian clocks and their relationship with the cellular redox state. In the third part of this work, the relationship between retinal damage and ROS is described. The last part of this work focuses on retinal degenerative pathology, age-related macular degeneration, and the relationships between this pathology, ROS, and light. Finally, the possible interactions between the retinal pigment epithelium (RPE), circadian rhythms, and this pathology are discussed.

Целью настоящей работы была оценка изменений зрительных функций у пациентов с возрастной макулярной дегенерацией (ВМД) и миопией средней и высокой степени на фоне лечения пептидным биорегулятором и поливитаминным комплексом. Материал и методы. Обследовано 60 пациентов (120 глаз) в возрасте
от 44 до 79 лет с возрастными изменениями сетчатки, разделенных на две группы в зависимости от вида лечения:
1-я группа — пациенты, получающие пептидный биорегулятор и поливитаминный комплекс; 2-я группа — пациенты, получающие только поливитаминный комплекс, а также на подгруппы в зависимости от длины ПЗО
(1-я подгруппа — с ПЗО < 26,5 мм; 2-я подгруппа — с ПЗО  26,5 мм). Оценивали изменения зрительных функций
на фоне лечения пептидным биорегулятором и поливитаминным комплексом. Результаты. Положительный ответ на предложенную терапию (повышение остроты зрения и улучшение периметрических показателей) зафиксирован у пациентов обеих групп с ПЗО < 26,5 мм, что можно объяснить исходно лучшим состоянием сетчатки.
У пациентов в подгруппе с ПЗО  26,5 мм отмечалось статистически достоверное улучшение остроты зрения
без коррекции, однако максимальная корригированная острота зрения осталась практически без изменений.
Заключение. Предложенная схема лечения может быть использована у пациентов с патологией сетчатки при
ВМД и миопии

Metformin and Macular Degeneration. JAMA March 11, 2021.
Thank you for your extensive study of metformin use and association with Macular Degeneration. The fact that you found that there was an inverse dose relationship with metformin use suggests to me that there is a confounding variable at play here. Also, that it is not metformin is not associated with MD reduction in diabetics supports this. Thus, the lower metformin doses are associated with milder diabetic disease, the higher metformin doses associated with more MD and worse diabetes, so, you are looking at not so much an inverse dose relationship (spurious) but an association between severity of diabetes and the development of MD. The current recommendations for the use  of metformin should remain the same. The use of metformin for the prevention of MD and other complications of aging, should be reserved for further study. Again, thank you. Gary Joseph Ordog, MD.

Original Investigation
January 21, 2021
Association of Metformin Use With Age-Related Macular Degeneration
A Case-Control Study.

Conclusion: Micronutrition is now part of the routine management of AMD for many ophthalmologists. Ophthalmologists choosing to use nutritional supplements are well-informed regarding current scientific studies.

Read this original research and sign up to receive Clinical Ophthalmology journal here: http://www.dovepress.com/articles.php?article_id=18712

В статье освещены современные аспекты этиологии и патогенеза развития дистрофических процессов сетчатки при миопии и возрастной макулярной дегенерации. Особое внимание уделено особенностям формирования хориоидальной неоваскуляризации в случае обеих патологий.

We investigated the concordance between
actual and declared content of the three macular carotenoids
in commercially available supplements aimed at
eye health. Three batches of nine products were tested for
content of lutein (L), zeaxanthin (Z) and meso-zeaxanthin
(MZ) by chiral HPLC–DAD. In every product tested,
actual L concentration was close to target, but Z concentration
varied greatly (47–248 % of declared concentration),
and the L:Z ratio within some supplements was adversely
affected in consequence. In six of seven products not
declaring MZ, we found this carotenoid, and four of them,
using the same L source, contained a concentration of MZ
that correlated positively and significantly with measured
concentrations of L (r2 = 0.86; P < 0.001). More transparency
is needed in terms of concordance between actual
and declared concentrations of Z in commercially available
formulations, and MZ should be declared in those formulations
where it is present.

Conclusion: Many of the eyes with hemorrhagic lesions showed stabilization or improvement of the mean BCVA after treatment within 1 year. Anti-VEGF treatment can be considered as a useful treatment option in eyes with hemorrhages secondary to nAMD.

Read this original research and sign up to receive Clinical Ophthalmology journal here: http://www.dovepress.com/articles.php?article_id=23303

Treatment of the neovascular form of age-related macular degeneration (AMD) has been revolutionized by the introduction of such agents as ranibizumab, bevacizumab, and aflibercept. As a result, the incidence of legal blindness occurring secondary to AMD has fallen dramatically in recent years in many countries. While these agents have undoubtedly been successful in reducing visual impairment and blindness, patients with neovascular AMD typically lose some vision over time, and often lose the ability to read, drive, or perform other important activities of daily living. Efforts are therefore under way to develop strategies that allow for earlier detection and treatment of this disease. In this review, we begin by providing an overview of the rationale for, and the benefits of, early detection and treatment of neovascular AMD. To achieve this, we begin by providing an overview of the pathophysiology and natural history of choroidal neovascularization, before reviewing the evidence from both clinical trials and "real-world" outcome studies. We continue by highlighting an area that is often overlooked: the importance of patient education and awareness for early AMD detection. We conclude the review by reviewing an array of both established and emerging technologies for early detection of choroidal neovascularization, ranging from Amsler chart testing, to hyperacuity testing, to advanced imaging techniques, such as optical coherence tomography.

SIGNIFICANCE: Head-mounted low vision devices have received considerable attention in recent years owing to rapidly developing technology, facilitating ease of use and functionality. Systematic clinical evaluations of such de- vices remain rare but are needed to steer future device development.
PURPOSE: The purpose of this study was to investigate, in a multicenter prospective trial, the short- and medium- term effects of a head-worn vision enhancement device (eSight Eyewear).
METHODS: Participants aged 13 to 75 years with stable vision (distance acuity, 20/60 to 20/400; visual field di- ameter >20°) were recruited across six sites. Data were collected at baseline (no device), at fitting (with device), and after 3 months of everyday use. Outcome measures were visual ability measured by the Veterans Affairs Low Vision Visual Functioning Questionnaire 48, distance acuity (Early Treatment Diabetic Retinopathy Study), reading performance (MNREAD chart), contrast sensitivity (MARS chart), face recognition, and a modified version of the Melbourne Low Vision Activities of Daily Living (ADL) Index.
RESULTS: Among the 51 participants, eSight introduction immediately improved distance acuity (0.74 ± 0.28 logMAR), contrast sensitivity (0.57 ± 0.53 log units), and critical print size (0.52 ± 0.43 logMAR), all P < .001, without any further change after 3 months; reading acuity improved at fitting (0.56 ± 0.35 logMAR) and by one ad- ditional line after 3 months, whereas reading speed only slightly increased across all three time points. The Melbourne ADL score and face recognition improved at fitting (P < .01) with trends toward further improvement at 3 months. After 3 months of use, Veterans Affairs Low Vision Visual Functioning Questionnaire 48 person measures (in logits) improved: overall, 0.84, P < .001; reading, 2.75, P < .001; mobility, 0.04, not statistically significant; visual in- formation, 1.08, P < .001; and visual motor, 0.48, P = .02.
CONCLUSIONS: eSight introduction yields immediate improvements in visual ability, with face recognition and ADLs showing a tentative benefit of further use. Overall, visual ability, reading, and visual information showed greatest benefit with device use. Further studies need to examine benefits of practice and training and possible dif- ferential effects of underlying pathology or baseline vision.

on behalf of the TREX-AMD Study Group* Purpose: To assess prospectively a treat-and-extend (TREX) management strategy compared with monthly dosing of intravitreal ranibizumab in treatment-naïve neovascular age-related macular degeneration (AMD) patients. Design: Phase IIIb, multicenter, randomized, controlled clinical trial. Participants: Sixty patients with treatment-naïve neovascular AMD randomized 1:2 to monthly or TREX management. Methods: Patients with Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) from 20/32 to 20/500 (Snellen equivalent) were randomized to receive intravitreal 0.5 mg ranibizumab monthly or according to a TREX protocol. The TREX patients were treated monthly for at least 3 doses, until resolution of clinical and spectral-domain optical coherence tomography evidence of exudative disease activity; the interval between visits then was individualized according to a strict prospective protocol. Main Outcome Measures: Mean ETDRS BCVA change from baseline. Results: At baseline, mean age was 77 years (range, 59e96 years), mean BCVA was 20/60 (Snellen equivalent), and mean central retinal thickness (CRT) was 511 mm. Fifty-seven eyes (95%) completed month 12, at which point mean BCVA improved by 9.2 and 10.5 letters in the monthly and TREX cohorts, respectively (P ¼ 0.60). The mean number of injections administered through month 12 was 13.0 and 10.1 (range, 7e13) in the monthly and TREX cohorts, respectively (P < 0.0001). Among TREX patients, 7 (18%) were maximally extended, 4 (10%) demonstrated fluid at every visit, and at month 12, 18 (45%) had achieved an extension interval of 8 weeks or more; the mean maximum extension interval between injections after the first 3 monthly doses was 8.4 weeks (range, 4e12 weeks). Most TREX patients who demonstrated recurrent exudative disease activity (17/24 [71%]) were unable to extend beyond their initial maximum extension interval. Conclusions: The TREX neovascular AMD management strategy used in this prospective, randomized, controlled trial resulted in visual and anatomic gains comparable with those obtained

Like many animals, humans are sensitive to the polarization of light. We can detect the angle of polarization using an entoptic phenomenon called Haidinger's brushes, which is mediated by dichroic carotenoids in the macula lutea. While previous studies have characterized the spectral sensitivity of Haidinger's brushes, other aspects remain unexplored. We developed a novel methodology for presenting gratings in polarization-only contrast at varying degrees of polarization in order to measure the lower limits of human polarized light detection. Participants were, on average, able to perform the task down to a threshold of 56%, with some able to go as low as 23%. This makes humans the most sensitive vertebrate tested to date. Additionally, we quantified a nonlinear relationship between presented and perceived polarization angle when an observer is presented with a rotatable polarized light field. This result confirms a previous theoretical prediction of how uniaxial corneal birefringence impacts the perception of Haidinger's brushes. The rotational dynamics of Haidinger's brushes were then used to calculate corneal retardance. We suggest that psychophysical experiments, based upon the perception of polarized light, are amenable to the production of affordable technologies for self-assessment and longitudinal monitoring of visual dysfunctions such as age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of vision loss in adults over 60 years old globally.
There are two forms of advanced AMD: “dry” and “wet”. Dry AMD is characterized by geographic atrophy of the
retinal pigment epithelium and overlying photoreceptors in the macular region; whereas wet AMD is characterized
by vascular penetrance from the choroid into the retina, known as choroidal neovascularization (CNV). Both
phenotypes eventually lead to loss of central vision. The pathogenesis of AMD involves the interplay of genetic
polymorphisms and environmental risk factors, many of which elevate retinal oxidative stress. Excess reactive
oxygen species react with cellular macromolecules, forming oxidation-modified byproducts that elicit chronic
inflammation and promote CNV. Additionally, genome-wide association studies have identified several genetic
variants in the age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1
(ARMS2-HTRA1) locus associated with the progression of late-stage AMD, especially the wet subtype. In this
review, we will focus on the interplay of oxidative stress and HTRA1 in drusen deposition, chronic inflammation,
and chronic angiogenesis. We aim to present a multifactorial model of wet AMD progression, supporting HTRA1
as a novel therapeutic target upstream of vascular endothelial growth factor (VEGF), the conventional target
in AMD therapeutics. By inhibiting HTRA1’s proteolytic activity, we can reduce pro-angiogenic signaling and prevent proteolytic breakdown of the blood-retina barrier. The anti-HTRA1 approach offers a promising alternative treatment option to wet AMD, complementary to anti-VEGF therapy.

Background: The induction of retinal pigmented epithelium cells (RPE) is one of the most important objectives in
research focused on treating retinal degenerative diseases. The present study aims to differentiate human adipose
stem cells (hADSCs) into RPE cells for replacement therapies in cases of retinal degenerative diseases.
Methods: Lipoaspirate-derived human adipose stem cells (LA-hADSCs) were obtained from abdominal samples
and examined by immunocytochemistry for the expression of mesenchymal adipose stem cell markers. RPE cells
were also obtained from human samples and cultured to be used as control after being examined for the expression
of their designated markers. hADSCs differentiated into RPE cells after 80 days using chemical inducers
in one steps. The differentiated cells were then compared to control cells in marker expression. The differentiated
cells were also examined under a scanning electron microscope for the presence of apical microvilli and cell
connection.
Results: Cultured hADSCs at the fourth passage was shown to express the surface markers CD90 (98 ± 2%),
CD11b (96 ± 3%), and CD105 (95 ± 4%). The RPE cells obtained from human samples expressed the marker
RPE65 quite well. 80 days after differentiation, the previously hADSCs expressed both RPE65 (100%) and
CRALBP (96 ± 1%) and were thus significantly similar to the RPE cells obtained from human samples.
Morphologically, differentiated cells appeared to have epithelial and cytoplasmic pigment granules.
Observations using a scanning electron microscope recorded clear connections among the differentiated RPE
cells and revealed apical microvilli.
Conclusion: Human adipose stem cells can differentiate into retinal pigmented epithelium cells, which can be
used in cell replacement therapy for degenerative diseases including age-related macular degeneration (AMD) as
well as retinitis pigmentosa (RP).

Background: To evaluate changes in central macular thickness (CMT) and visual outcome in patients with neovascular age-related macular degeneration (AMD) treated initially with bevacizumab and subsequently switched to either aflibercept or ranibizumab. Methods: Observational clinical study was performed. We measured the structural outcome (CMT on SD-OCT; μm) and the visual outcome (best corrected visual acuity (BCVA); logMAR), as follows: before treatment (at baseline), following bevacizumab treatment (switch follow-up) and after switching from bevacizumab to aflibercept-or ranibizumab treatment (final follow-up, AG/, RG).

Age-related macular degeneration (AMD) is an ocular disorder that affects the elderly. The prevalence of AMD is growing due to the aging population in society; hence early diagnosis is necessary to prevent vision loss in the elderly. Arranging a detailed eye screening system for detecting AMD is a very challenging process. This paper proposes a novel multiscale convolutional neural network (CNN) architecture for accurate diagnosis of AMD. The architecture proposed is a multiscale CNN with seven convolutional layers for classifying AMD or normal images. The multiscale convolution layer enables a large number of local structures to be generated with various filter sizes. In this proposed network, the sigmoid function is used as the classifier. The proposed CNN network is trained on the Mendeley dataset and tested on four datasets, namely Mendeley, OCTID, Duke, SD-OCT Noor dataset and achieved an accuracy of 99.73%, 98.08%, 96.66%, and 97.95% respectively. Comparison with alternative methods yielded results that exhibit the efficiency of the proposed algorithm in AMD detection. Even if the proposed model is trained only on the Mendeley dataset, it achieved good detection accuracy when tested with other datasets. This indicates the proposed model's ability to classify AMD/Normal images from other datasets. Comparison with other approaches produced results that exhibit the efficiency of the proposed algorithm in detecting AMD. The proposed architecture can be applied in rapid screening of the eye for the early detection of AMD. Due to less complexity and fewer learnable parameters, the proposed CNN can be implemented in real-time.

Цель работы—выявление связи между структурно-анатомическими изменениями глазного яблока при возрастной макулярной дегенерации и миопии средней и высокой степени, а также поиск взаимосвязи между разными типами миопических стафилом и изменениями зрительных функций.

Известно что условное перепрограммирование эпителиальных клеток обеспечивается комбинацией ингибитора ROCK и растворимых факторов, высвобождаемых при апоптозе питающих клеток под действием радиации. В данной статье обсуждается возможность замены этих факторов ингибиторами фермента 5-LOX .

What must happen so that people like me, who are visually impaired, can work more efficiently is a standardization of the website layout with each category, e.g. citation should always be in the upper left corner and have an orange button, the Download button must be in the center and of light green color with black letters in it, etc.


I find it challenging to gather all information from research articles because every provider of online scientific publications has its own layout, its own functionalities, its own format, etc. But instead of me having to remember the location of each functionality for each provider, it would be much better if all providers would use the same general layout, color coding and a minimum set of function to which each provider is welcome to add whatever deemed beneficial.


E.g. here in ResearchGate it is hard for me to find the "Message" button with my Zoomtext because it is of the same color as the background and the only way to recognize it is by the thin blue letters spelling the word "Message". Even though Academia.edu and ResearchGate.net serve the same purpose, there are a lot of differences in navigating through their sites. Therefore, providers of similar content and functions should be required to offer a user interface option that follows the same standards regarding layout, coloring, contrast enhancing, screen-reader accessibility and other accessibility functions because that way sensory impaired people must only learn once, e.g. how to access scientific journals, figures, citations, supplementary material, PDF files, etc.


Knowledge-exchange and online employment websites must provide an interface for its users to interact. All providers of such kind of interaction interfaces should be required to provide a disability communication mode, which must adhere to strict standards pertaining to accessibility, layout, color coding, use of functions like "Search", "Submit", "Download", "Message Exchange", "User Lookup", etc. Each provider should be free to choose its own communication interface features, which don't need to be standardized to maintain options for commercial innovations, but that must be in addition but never instead a clutter-free interface that allows accessing the same kind of information always the same way across all provider platforms.


Each provider of any kind of web-based functions or services must provide the option to chose any older legacy version of its software, cloud or browser-based functions so that in 20 years I can still use the same method to accomplish the same things as today.

Age-related macular degeneration (AMD) is a major cause of blindness and is associated with complement dysregulation. The disease is a potential target for stem cell therapy but success is likely to be limited by the inflammatory response. We investigated the innate immune properties of human induced-pluripotent stem cell (iPSC)-derived RPE cells, particularly with regard to the complement pathway. We focused on collectin-11 (CL-11), a pattern recognition molecule that can trigger complement activation in renal epithelial tissue. We found evidence of constitutive and hypoxia-induced expression of CL-11 in iPS-RPE cells, and in the extracellular fluid. Complement activation on the cell surface occurred in conjunction with CL-11 binding. CL-11 has been shown to activate inflammatory responses through recognition of L-fucose, which we confirmed by showing that fucosidase-treated cells, largely, failed to activate complement. The presence of CL-11 in healthy murine and human retinal tissues confirmed the biological relevance of CL-11. Our data describe a new trigger mechanism of complement activation that could be important in disease pathogenesis and therapeutic interventions. The retinal pigment epithelium (RPE) consists of a monolayer of cells situated between the photoreceptor cells and the choroid and plays a critical role in the visual cycle, maintaining the health of photoreceptor cells by providing nutrients, growth factors and by continually phagocytosing photoreceptor outer segment discs. Together with Bruch's membrane, tight junctions between neighboring RPE cells form the outer blood-retinal barrier, which is essential for maintaining retinal homeostasis. Loss of RPE cells and the subsequent loss of photoreceptor cells they support is associated with degenerative diseases such as Stargardt's disease, retinitis pigmentosa and age-related macular degeneration (AMD), the leading cause of blindness in the developed world 1. Current therapies for AMD are only effective in reducing aberrant blood vessel formation in neovascular AMD and there is no therapy for geographic atrophy, an advanced non-vascular form that comprises a third of all late-stage AMD patients 2. A growing body of evidence suggests that choroidal blood flow is reduced in AMD 3,4 and data from transgenic mouse models where HIF (hypoxia-inducible factor) pathways are specifically activated in RPE show photoreceptor degeneration and features consistent with some aspects of AMD pathology 5. As HIF pathways are linked to inflammation 6 it is possible that some of the chronic dysregulation of local para-inflammatory responses in the eye associated with AMD 7–9 may be driven by RPE hypoxic stress resulting in the aberrant activation of complement on host cells. Regrettably, how complement system dysregulation in retina can lead to cell and tissue damage under inflammatory conditions, including AMD, has not yet been addressed. Circulating levels of C3a, C3d and C5a, have been found in AMD patients 10,11 indicating enhanced local complement activation. Moreover, polymorphisms in a number of complement genes such as, CFH, C3, CFB and C2, have been shown to be associated with AMD 12–14 suggesting that the complement system, in particular the alternative pathway, may be dys-regulated in AMD patients. Therefore, appropriate control of local complement activation may preserve retinal

Age-related macular degeneration (AMD) is the leading cause of central vision loss worldwide. Loss of retinal pigment epithelium (RPE) is a major pathological hallmark in AMD with or without pathological neovascularization. Although activation of the immune system is implicated in disease progression, pathological pathways remain diverse and unclear. Here, we report an unexpected protective role of a pro-inflammatory cytokine, interleukin-33 (IL-33) in ocular angiogenesis. IL-33 and its receptor (ST2) are expressed constitutively in human and murine retina and choroid. When RPE was activated, IL-33 expression was markedly elevated in vitro. We found that IL-33 regulated tissue remodelling by attenuating wound-healing responses, including reduction in migration of choroidal fibroblasts and retinal microvascular endothelial cells, and inhibition of collagen gel contraction. In vivo, local administration of recombinant IL-33 inhibited murine choroidal neovascularization (CNV) formation, a surrogate of human neovascular AMD, and this effect was ST2-dependent. Collectively, these data demonstrate IL-33 as a potential immunotherapy and distinguishes pathways for subverting AMD pathology.