Current evidence suggests that exposure to chronically induced intraocular pressure (IOP) leads to neurodegenerative changes in the inner retina. This study aimed to determine
retinal proteomic alterations in a rat model of
glaucoma and compared findings with human
retinal proteomics changes in
glaucoma reported previously. We developed an experimental
glaucoma rat model by subjecting the rats to increased IOP (9.3 ± 0.1 vs 20.8 ± 1.6 mm Hg) by weekly
microbead injections into the eye (8 weeks). The
retinal tissues were harvested from control and glaucomatous eyes and
protein expression changes analysed using a multiplexed quantitative proteomics approach (TMT-MS3). Immunofluorescence was performed for selected
protein markers for data validation. Our study identified 4304
proteins in the rat retinas. Out of these, 139
proteins were downregulated (≤0.83) while the expression of 109
proteins was upregulated (≥1.2-fold change) under
glaucoma conditions (P ≤ .05). Computational analysis revealed reduced expression of
proteins associated with
glutathione metabolism,
mitochondrial dysfunction/oxidative phosphorylation, cytoskeleton, and actin filament organisation, along with increased expression of
proteins in coagulation cascade, apoptosis, oxidative stress, and RNA processing. Further functional network analysis highlighted the differential modulation of
nuclear receptor signalling, cellular survival,
protein synthesis, transport, and cellular assembly pathways. Alterations in
crystallin family,
glutathione metabolism, and
mitochondrial dysfunction associated
proteins shared similarities between the animal model of
glaucoma and the human disease condition. In contrast, the activation of the classical complement pathway and upregulation of
cholesterol transport proteins were exclusive to human
glaucoma. These findings provide insights into the neurodegenerative mechanisms that are specifically affected in the retina in response to chronically elevated IOP.