Novel Glaucoma Therapy Rescuing Excitotoxicity in An Ischemia-Reperfusion Mice Model
Journal
Progress in Biomedical Optics and Imaging Proceedings of SPIE
Series/Report No.
Progress in Biomedical Optics and Imaging Proceedings of SPIE
Journal Volume
13297
Start Page
132970B
ISBN
[9781510683426]
Date Issued
2025-01-01
Author(s)
Abstract
Glaucoma, a leading cause of irreversible blindness, is characterized by a progressive degeneration of retinal ganglion cells (RGCs). While current therapies primarily focus on reducing intraocular pressure (IOP), they provide limited protection against retinal excitotoxicity which is a key contributor to retinal neuronal loss. Excitotoxicity arises from an imbalance between excitatory glutamatergic and inhibitory GABAergic transmission systems (E/I imbalance). This study aims to target excitotoxicity via modulating E/I imbalance within the retina as a potential therapeutic approach to minimize physical damage in glaucoma. Using an ischemia-reperfusion (IR) mouse model, we induced elevated intraocular pressure (IOP) in the right eyes of ICR mice to mimic acute glaucoma with their left eyes as internal controls. An excitotoxic modulator was administered to the treatment group of mice 10 minutes after IR damage, while the control group received only the vehicle. One week after IR damage, the retinal morphology and RGC numbers of mice were quantified using hematoxylin and eosin staining and immunohistochemistry. Their damaged right eyes had reduced retinal thickness, especially in the nuclear layers (ONL and INL) as well as the inner plexiform layer (IPL), and fewer RGC numbers compared to control left eyes. In the treatment group, the right eyes exhibited better preservation of retinal structures and less retinal neuronal loss, compared to the vehicle-control group. These results highlight the neuroprotective role of a modulator in mitigating retinal degeneration under elevated IOP conditions. Therefore, modulating E/I imbalance represents a promising therapeutic approach for glaucoma by protecting against retinal excitotoxicity. © 2025 SPIE.
Type
conference paper