Abstract
Purpose :
Since glaucoma pathophysiology are still not very well understood, experimental animal models are important to investigate structural and molecular alterations, and search for neuroprotective agents. In this study, we characterize the viability, clinical repercussions and the morphofunctional changes of a model of glaucoma based on double full-circle cauterization (DC) of the limbal vascular plexus.
Methods :
2–3-month-old Lister hooded rats were submitted to two 360 degrees limbic plexus cauterization, apart 14 days from each other. Low-temperature ophthalmic cautery was used in the procedure. Naive animals were used as controls. IOP was measured by TonoLab®. In-vivo morphofunctional evaluations were assessed by optical coherence tomography, fundoscopy, pattern-electroretinogram (PERG) and Optomotry®. Moreover, two weeks after DC, animals were euthanized and retinas were immunostained for RBPMS to evaluate retinal ganglion cells (RGCs) degeneration. Statistics were assessed using unpaired t-test with Welch’s correction in GraphPad Prism 8.01 software.
Results :
DC led to an immediate increase in IOP in injured eyes, reaching its peak on the day after the procedure, followed by a decline until reaching normality on the ninth day after lesion. The second IOP peak (49.3±5.31 mmHg; n=6; p<0.05) was higher in relation to the first intervention (39.4±1.52 mmHg; n=6). Furthermore, ocular hypertension (OHT) caused severe structural damage regionally to the superior and temporal retina, and resulted in increased optic nerve cupping (n=6). Such alterations were accompanied by RGCs electrophysiological dysfunction (amplitude of 9.81±0.16 µV [naive; n=5] and 3.34±0.62 µV [DC; n=6] when submitted to 0.018 cpd spatial frequency on PERG; p<0.001) and optomotor reflex reduction (spatial frequency of 0.66±0.01 cpd [naive; n=5] and 0.26±0.09 cpd [DC; n=6]; p<0.01). Yet, RGCs density was 609±224.7 cells/mm2 (n=6; p<0.001) 14 days after DC compared to 2246±50.5 cells/mm2 (n=5) in naive retinas, representing an average loss of 72.8% of this cell type. The magnitude of RGCs degeneration is highly dependent on the pressure load caused by the insult.
Conclusions :
Here, we demonstrated the viability of DC of the limbal vascular plexus to induce OHT in pigmented rats. This model provides RGCs degeneration, functional and behavioral impairments, and also structural changes that resemble pathogenic alterations found in glaucoma.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.