Background: The neovascular aged-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly. It is presently treated by anti-VEGF intravitreal injection in order to stop the neovascularization. In seeking of more efficient treatments to prevent retinal damage, it has been proposed that the kinin-kallikrein system (KKS), a key player in inflammation, could be involved in AMD etiology. However, the role of kinin receptors and their interaction with VEGF in AMD is poorly understood.
Methods: In order to address this question, choroidal neovascularization (CNV) was induced in the left eye of Long-Evans rat. After laser induction, anti-VEGF or IgG control were injected into the vitreal cavity. Gene expression was measured by qRT-PCR, retinal adherent leukocytes were labelled with FITC-Concanavalin A lectin, vascular leakage by the method of Evans blue and cellular localisation by immunohistochemistry.
Results: The number of labelled adherent leucocytes was significantly increased in laser-induced CNV compared to the control eye. This was significantly reversed by one single injection of anti-VEGF. Extravasation of Evans blue dye was significantly increased in laser-induced CNV eyes compared to control eyes and partially reversed by one single injection of anti-VEGF or by R954 treatment. The mRNA expression of inflammatory mediators was significantly increased in the retina of CNV rats. Immunodetection of B1R was significantly increased in CNV eyes. B1R immunolabeling was detected on endothelial and ganglion cells.
Conclusions: This study is the first to highlight an effect of the kinin/kallikrein system in a model of CNV that could be reduced by both anti-VEGF therapy and topically administered B1R antagonist R-954.
Abstract: Subretinal inflammation plays a critical role in retinal degenerative diseases. Although activated macrophages have been shown to play a key role in the progression of retinopathies and specifically in age-related macular degeneration, little is known about the mechanisms involved in the loss of photoreceptors leading to vision impairment. In our study on retinal damages induced by photo-oxidative stress, we have observed that CD36-deficient mice featured less subretinal macrophage accumulation with attenuated photoreceptor degeneration compared to wild-type (WT) mice. Treatment with CD36-selective azapeptide ligand (labelled MPE-001) as modulator of the inflammatory environment of the retina reduced subretinal macrophage/activated microglia accumulation with preservation of photoreceptor layers and function assessed by ERG in WT, in a CD36-dependent manner. The azapeptide modulated the transcriptome of subretinal macrophage/activated microglia by reducing pro-inflammatory markers. In isolated macrophages, the CD36-selective azapeptide induced dissociation of the CD36-TLR2/6 heterodimer complex (using FRET) altering the TLR2 signaling pathway, thus decreasing NF-KB activation and inflammasome activity. The azapeptide also incurred cytoprotection against photoreceptor apoptosis elicited by activated macrophages. These findings suggest that the azapeptide as ligand of co-receptor CD36 decreases the inflammatory response by modulating CD36-TLR2/6 complex signaling pathway in macrophages, and suggests its potential application in the treatment of retinal degenerative diseases.
Abstract: Pediatric neuro-ophthalmology is a subspecialty within neuro-ophthalmology. Pediatric neuro-ophthalmic diseases must be considered separate from their adult counterparts, due to the distinctive nature of the examination, clinical presentations, and management choices. This manuscript will highlight four common pediatric neuro-ophthalmic disorders by describing common clinical presentations, recommended management, and highlighting recent developments. Diseases discussed include pediatric idiopathic intracranial hypertension (IIH), pseudopapilledema, optic neuritis (ON) and optic pathway gliomas (OPG). The demographics, diagnosis and management of common pediatric neuro-ophthalmic disease require a working knowledge of the current research presented herein. Special attention should be placed on the differences between pediatric and adult entities such that children can be appropriately diagnosed and treated.
Abstract: Complications of myopia have become an important public health issue with serious socio-economic burdens. Prevention and treatment are both important. The Taiwan Student Vision Care Program (TSVCP) promoted by Ministry of Education (MOE) has been carried out for 3 decades in Taiwan. The myopia prevalence has increased rapidly to a high level and therefore myopia prevention has continued to be the most important item in the program. Therefore, TSVCP aims to decrease the prevalence of myopia, in order to decrease the high myopia related blindness in the future. Recently, outdoor activity has been found to be an important protective factor for myopia and was implemented in TSVCP since 2010. Afterwards, the nationwide vision impairment rate (uncorrected vision 20/25 or less) of elementary school students declined unprecedentedly and continuously in recent years. Evidence-based protective and risk factors for myopia are now clearer. Widespread acknowledgement of myopic disease, preventing the onset of myopia, prompt diagnosis, and early treatment to control progression are all important.
Abstract: Successful management of a case of aggressive posterior retinopathy of prematurity (APROP) poorly responsive to laser therapy with intravitreal bevacizumab (IVB) is discussed. IVB is useful as rescue therapy in such cases, if given within the correct window period post laser therapy.
