Therapeutic Interventions against Inflammatory and Angiogenic Mediators in Proliferative Diabetic Retinopathy

The global prevalence of diabetes is estimated to be 336 million people, with diabetic complications contributing to significant worldwide morbidity and mortality. Diabetic retinopathy results from cumulative microvascular damage to the retina and inflammation is recognized as a critical driver of this disease process. This paper outlines the pathophysiology leading to proliferative diabetic retinopathy and highlights many of the inflammatory, angiogenic, and cytokine mediators implicated in the development and progression of this disease. We focus a detailed discussion on the current targeted therapeutic interventions used to treat diabetic retinopathy

RIP Kinase-Mediated Necrosis as an Alternative Mechanism of Photoreceptor Death

Photoreceptor cell death is the terminal event in a variety of retinal disorders including age-related macular degeneration, retinitis pigmentosa, and retinal detachment. Apoptosis has been thought to be the major form of cell death in these diseases, however accumulating evidence suggests that another pathway, programmed necrosis is also important. Recent studies have shown that, when caspase pathways are blocked, receptor interacting protein (RIP) kinases promote necrosis and overcome apoptosis inhibition. Therefore, targeting of both caspase and RIP kinase pathways are required for effective photoreceptor protection. Here, we summarize the current knowledge of RIP kinase-mediated necrotic signaling and its contribution to photoreceptor death

Mechanisms of Inflammation in Proliferative Vitreoretinopathy: From Bench to Bedside

Proliferative vitreoretinopathy (PVR) is a vision-threatening disease and a common complication of surgery to correct rhegmatogenous retinal detachment (RRD). Several models of the pathogenesis of this disease have been described with some of these models focusing on the role of inflammatory cells and other models focusing on the role of growth factors and cytokines in the vitreous which come into contact with intraretinal and retinal pigment epithelial cells. New experiments have shed light on the pathogenesis of PVR and offer promising avenues for clinical intervention before PVR develops. One such target is the indirect pathway of activation of platelet-derived growth factor receptor alpha (PDGRα), which plays an important role in PVR. Clinical trials assessing the efficacy of 5-fluorouracil (5-FU) and low-molecular-weight heparin (LMWH), daunorubicin, and 13-cis-retinoic acid, among other therapies, have yielded mixed results. Here we review inflammatory and other mechanisms involved in the pathogenesis of PVR, we highlight important clinical trials, and we discuss how findings at the bench have the potential to be translated to the bedside

Retinal Detachment Model in Rodents by Subretinal Injection of Sodium Hyaluronate

Subretinal injection of sodium hyaluronate is a widely accepted method of inducing retinal detachment (RD)1-15. However, the height and duration of RD or the occurrence of subretinal hemorrhage can affect photoreceptor cell death in the detached retina16-21. Hence, it is advantageous to create reproducible RDs without subretinal hemorrhage for evaluating photoreceptor cell death. We modified a previously reported method to create bullous and persistent RDs in a reproducible location with rare occurrence of subretinal hemorrhage. The critical step of this modified method is the creation of a self-sealing scleral incision, which can prevent leakage of sodium hyaluronate after injection into the subretinal space. To make the self-sealing scleral incision, a scleral tunnel is created, followed by scleral penetration into the choroid with a 30 G needle. Although choroidal hemorrhage may occur during this step, astriction with a surgical spear reduces the rate of choroidal hemorrhage. This method allows a more reproducible and reliable model of photoreceptor death in diseases that involve RD such as rhegmatogenous RD, retinopathy of prematurity, diabetic retinopathy, central serous chorioretinopathy, and age-related macular degeneration (AMD)

Choroidal Neovascular Membrane Formation and Retinochoroidopathy in a Patient with Systemic Langerhans Cell Histiocytosis: A Case Report and Review of the Literature

We report a case of bilateral atrophic retinochoroidopathy with choroidal neovascular membrane (CNVM) formation in a patient with systemic Langerhans cell histiocytosis (LCH). A 35-year-old female, diagnosed with LCH at the age of 3, experienced an episode of acute vision loss in her right eye. Visual acuity was counting fingers. Dilated fundus exam and fluorescein angiography revealed the presence of CNVM along with bilateral widespread areas of chorioretinal atrophy. The patient underwent removal of CNVM with excellent postoperative visual acuity (20/25); however, indolent progression of her disease led to gradual deterioration of visual acuity (20/80 in the right eye and 20/320 in the left). This case shows that in contrast to previous reports, intraocular involvement of LCH does not need to be dramatic and clinically evident but it can acquire a chronic degenerative form. This report aims to raise awareness among ophthalmologists concerning the potential intraocular sequelae of LCH

Advances in Age-related Macular Degeneration Understanding and Therapy

While the development of anti-vascular endothelial growth factor (anti-VEGF) as a therapy for neovascular age-related macular degeneration (AMD) was a great success, the pathologic processes underlying dry AMD that eventually leads to photoreceptor dysfunction, death, and vision loss remain elusive to date, with a lack of effective therapies and increasing prevalence of the disease. There is an overwhelming need to improve the classification system of AMD, to increase our understanding of cell death mechanisms involved in both neovascular and non-neovascular AMD, and to develop better biomarkers and clinical endpoints to eventually be able to identify better therapeutic targets—especially early in the disease process. There is no doubt that it is a matter of time before progress will be made and better therapies will be developed for non-neovascular AMD