Abstract
Purpose :
Caveolin-1 (Cav-1) mediates the neurovascular coupling (NVC) response in the eye, which is disrupted in glaucoma patients. In this study, we investigated the effect of lentivirus-mediated gene therapy with Cav-1 on NVC at the optic nerve head (ONH) and retinal blood vessel structure and function.
Methods :
Lentiviral vectors encoding Cav-1 (Cav-1_LV) or control lentivirus particles (Control_LV) were delivered via intraocular injection to 13 week-old Cav-1 knockout (Cav-1 KO) mice. The NVC response to light stimulus and positive scotopic threshold response (pSTR) in retinal ganglion cells were measured 4-weeks after injection. Intraocular pressure (IOP) was measured at baseline, 2 and 4-weeks after injection. Cav-1 expression in the retina and changes to retinal blood vessels were visualized by immunostaining.
Results :
Cav-1_LV effectively improved the NVC response to light flicker stimulus in Cav-1 KO mice within peripapillary vessels (arteries 1.03 ± 0.04 vs 0.90 ± 0.04 AU, p = 0.048; veins 1.0 ± 0.03 vs 0.89 ± 0.05 AU, p = 0.04), ONH small vessels (1.1 ± 0.03 vs 0.93 ± 0.04 AU, p = 0.01) and neuroretinal tissue (1.1 ± 0.04 vs 0.9 ± 0.04 AU, p=0.004) as compared to Control_LV treated eyes. Cav-1 transduction appeared mostly in the retinal vessels, although gross retinal blood vessel morphology was not altered. However, extravasation of albumin in retinal blood vessels was reduced following Cav-1_LV injection (p<0.001). pSTR measurements appeared higher in Cav-1_LV compared to Control_LV-treated eyes although this did not reach statistical significance. There was no significant difference in post-treatment IOP between groups.
Conclusions :
Lentiviral gene therapy with Cav-1 improves the NVC response at the optic nerve head. This may be mediated by improved endothelial function in the retinal microvasculature.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.