Abstract
Purpose :
To identify the effects of RIPA-56 in ischemic insult and its molecular mechanism in a rodent model of anterior ischemic optic neuropathy (rAION)
Methods :
AION induction was performed using an argon laser for photoactivation after the intravenous administration of rose bengal via the tail vein. Male Wistar rats were divided into four groups: (1) Sham; (2) AION induction with subcutaneous administration of phosphate-buffered saline (PBS); (3) AION induction with subcutaneous administration of RIPA-56 (15 mg/kg) solution; (4) AION induction with subcutaneous administration of RIPA-56 (30 mg/kg) solution. Rats were humanely euthanized one month post-infarction. The investigative procedures encompassed Flash Visually Evoked Potential (FVEP), Fluoro-Gold (FG) retrograde labeling of retinal ganglion cells (RGCs), Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and immunohistochemical examinations of ED1, Ym1, and Iba1 in both the optic nerve (ON) and retina to assess visual functionality. Western blotting analysis was conducted to explore underlying signaling pathways.
Results :
The FVEP assessment demonstrated that the administration of RIPA-56 significantly restored visual function compared to the PBS treatment group after AION induction. The FG retrograde labeling experiment improved the survival of retinal ganglion cells (RGCs) in the RIPA-56 treated group compared to the PBS treatment group after AION induction. Immunohistochemical studies of ED1 suggested a decrease in ED1-positive cells and an increase in Ym1-positive cells in the optic nerve (ON) of the RIPA-56 treatment group after ischemic injury. Furthermore, the TUNEL assay and immunohistochemical staining indicated improvements, with decreased TUNEL- and Iba1-positive cells in the retina of the RIPA-56 treatment group.
Conclusions :
These data suggest that the neuroprotective effects of RIPA-56 on RGCa survival and visual function during ischemic insult may be related to the anti-inflammatory and anti-apoptotic pathways. Our results support the potential of RIPA-56 as a novel treatment strategy for ischemic optic neuropathies.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.