Prolonged elevation of intraocular pressure results in retinal ganglion cell loss and abnormal retinal function in mice

Abstract

The purpose of this study was to assess the impact of prolonged intraocular pressure (IOP) elevation on retinal anatomy and function in a mouse model of experimental glaucoma. IOP was elevated by anterior chamber injection of a fixed combination of polystyrene beads and sodium hyaluronate, and maintained via re-injection after 24 weeks. IOP was measured weekly with a rebound tonometer for 48 weeks. Histology was assessed with a combination of retrograde labeling and antibody staining. Retinal physiology and function was assessed with dark-adapted electroretinograms (ERGs). Comparisons between bead-injected animals and various controls were conducted at both 24 and 48 weeks after bead injection. IOP was elevated throughout the study. IOP elevation resulted in a reduction of retinal ganglion cell (RGCs) and an increase in axial length at both 24 and 48 weeks after bead injection. The b-wave amplitude of the ERG was increased to the same degree in bead-injected eyes at both time points, similar to previous studies. The positive scotopic threshold response (pSTR) amplitude, a measure of RGC electrical function, was diminished at both 24 and 48 weeks when normalized to the increased b-wave amplitude. At 48 weeks, the pSTR amplitude was reduced even without normalization, suggesting more profound RGC dysfunction. We conclude that injection of polystyrene beads and sodium hyaluronate causes chronic IOP elevation which results in phenotypes of stable b-wave amplitude increase and progressive pSTR amplitude reduction, as well as RGC loss and axial length elongation.

Phenotypic and Functional Characterization of Müller Glia Isolated from Induced Pluripotent Stem Cell-Derived Retinal Organoids: Improvement of Retinal Ganglion Cell Function upon Transplantation

“…This model mimics the pathological features of RGC damage observed in glaucoma and is a reliable model of RGC damage which can be easily assessed by measuring the nSTR response of the ERG . Following NMDA damage, we observed a reduction in the nSTR and a slight elevation in the b‐wave of the ERG, which is characteristic of similar glaucoma models . We observed a partial but significant restoration of the nSTR after transplantation of the highest dose of cells used (1 × 10 5 ).…”

Elevated intracranial pressure causes optic nerve and retinal ganglion cell degeneration in mice

“…IOP was recorded using a rebound tonometer optimized for mouse use (Tonolab) under isoflurane anesthesia as previously described (Frankfort et al, 2013; Khan et al, 2015; Pease et al, 2011). …”

Crocin protects retinal ganglion cells against H2O2-induced damage through the mitochondrial pathway and activation of NF-κB

“…The hallmark of glaucoma is the apoptosis of retinal ganglion cells (RGCs), which are the only efferent neurons that convey visual signals from the retina to the brain. Several risk factors, including elevated intraocular pressure (2), oxidative stress (3), elevated glutamate (4) and aging (5), have been considered to accelerate RGC apoptosis in glaucoma, among which, oxidative stress is considered as the final common pathway in glaucoma (6). Several studies have reported that oxidative stress can lead to apoptosis of RGCs through activation of the mitochondrial pathway (7), and that apoptosis is the main cause of RGC loss (8).…”