The interphotoreceptor matrix (IPM) is a highly organized structure with interconnected domains surrounding cone and rod photoreceptor cells and extends throughout the subretinal space. Based on known roles of the extracellular matrix in other tissues, the IPM is thought to have several prominent functions including serving as a receptor for growth factors, regulating retinoid transport, participating in cytoskeletal organization in surrounding cells, and regulation of oxygen and nutrient transport. In addition, a number of studies suggest that the IPM also may play a significant role in the etiology of retinal degenerative disorders. In this review, we describe the present knowledge concerning the structure and function of the IPM under physiological and pathological conditions.

In the physiological condition, glutamate acts as an excitatory neurotransmitter in the retina. However, excessive glutamate can be toxic to retinal neurons by overstimulation of the glutamate receptors. Glutamate excess is primarily attributed to perturbation in the homeostasis of the glutamate metabolism. Major pathway of glutamate metabolism consists of glutamate uptake by glutamate transporters followed by enzymatic conversion of glutamate to nontoxic glutamine by glutamine synthetase. Glutamate metabolism requires energy supply, and the energy loss inhibits the functions of both glutamate transporters and glutamine synthetase. In this review, we describe the present knowledge concerning the retinal glutamate metabolism under the physiological and pathological conditions.

Purpose: To study lamina cribrosa (LC) depth variation measured by spectral-domain optical coherence tomography (SD-OCT) in four glaucomatous optic disc phenotypes. Methods: In this cross-sectional study, 59 normal eyes and 180 open-angle glaucoma (OAG) eyes were grouped into 56 focally injured discs (FI), 30 generalized enlargement of the optic cup discs (GE), 69 myopic glaucomatous discs (MY), and 25 senile sclerotic discs (SS). They were imaged by enhanced depth imaging SD-OCT, obtaining multiple horizontal and vertical optic disc B-scans. Mean and maximum LC depths were measured relative to Bruch's membrane opening (BMO) and the anterior sclera (AS) reference planes. Lamina cribrosa depths were compared between and among the normal and OAG group disc phenotypes. Lamina cribrosa depth differences within groups were examined as well as the overlap between them. Results: Mean and maximum LC depths relative to the BMO and AS reference planes were greater in the OAG group than in the normal group (P < 0.0001). Among glaucomatous phenotypes, the GE group had the greatest (P < 0.001) and the SS group had the smallest (P < 0.05) mean and maximum LC depths. There was a wide range of LC depth overlap between the normal and SS groups, and a high proportion of SS eyes had LC depths within the 95% confidence interval of the normal group. Conclusions: The LC was displaced posteriorly in OAG group compared to the normal group. The LC depth was significantly different among four glaucomatous disc phenotypes. The LC depth of the SS group was similar to the normal group.

A wide variety of animal models have been used to study glaucoma. Although these models provide valuable information about the disease, there is still no ideal model for studying glaucoma due to its complex pathogenesis. Animal models for glaucoma are pivotal for clarifying glaucoma etiology and for developing novel therapeutic strategies to halt disease progression. In this review paper, we summarize some of the major findings obtained in various glaucoma models and examine the strengths and limitations of these models.

In an ex vivo rat glaucoma model using dissected retinas, the neurosteroid allopregnanolone (AlloP) protects retinal ganglion cells (RGCs) via GABR/GABA_A receptors. To determine the involvement of macroautophagy/autophagy in neuroprotection by AlloP, we examined the effects of autophagy activators, rapamycin and torin 2, and autophagy inhibitors, bafilomycin A₁ and SAR405, on retin al morphology and expression of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 beta) and SQSTM1 (sequestosome 1). Administration of rapamycin or torin 2 exerted partial histological neuroprotection, while combined administration of AlloP with bafilomycin A₁ or SAR405 induced severe degeneration in a hyperbaric condition. Electron microscopic analyses showed that the addition of AlloP significantly increased autophagosomes and degenerative autophagic vacuoles in the retinal nerve fiber layer. Immunoblotting showed that the addition of AlloP or autophagic activators increased the lipidated form of LC3B (LC3B-II) and suppressed SQSTM1. Moreover, bafilomycin A₁ increased LC3B-II and SQSTM1 protein levels in the presence of AlloP without changes in corresponding mRNAs compared to AlloP-treated retinas in a hyperbaric condition. These data indicate that AlloP likely induces a protective form of autophagy in this model. In an in vivo rat model of glaucoma, we also observed neuroprotective effects of AlloP. Injection of polystyrene microbeads into the anterior chamber increased intraocular pressure about 3-fold and induced RGC apoptosis. A single intravitreal injection of AlloP or autophagy activators prevented apoptosis and protected RGCs with autophagy activation. We conclude that AlloP may serve as a potential therapeutic agent for the treatment of glaucoma via diverse mechanisms.