Abstract
Purpose :
Efforts to characterize the effects of mild ocular hypertension (mOHT) have revealed both capillary plexus-specific vascular phenotypes and upregulation of hypoxia inducible factor 1 alpha (Hif1α) in amacrine cells (ACs), each of which occurs prior to RGC loss. Importantly, AC-specific Hif1α plays a role in intermediate retinal capillary plexus (IRCP) development. Here, we aim to address the role of AC-specific Hif1α in mOHT.
Methods :
Hif1α conditional knockout animals (Hif1α cKO) were generated by crossing transgenic mice expressing Cre in ACs (Ptf1α-Cre) with Hif1α floxed mice. For all experiments, age-matched Cre-negative littermate controls were used.
mOHT was induced by injecting microbeads unilaterally while the fellow eye served as a non-injected control. IOP was measured three times weekly. Retinas were dissected 2 weeks post-injection. Retinas were immunostained with CD31 (endothelium) and COLIV (vascular basement membrane) for vascular analysis. BRN3a was used to assess RGC density.
Results :
Non-injected Hif1α cKO retinas showed significant deficits in IRCP junction density, vessel length, and vessel area compared to controls, confirming previous reports. Injected Hif1α cKO eyes achieved a 34% increase in IOP. Similar to published reports, there was no difference in RGC counts following mOHT. Unlike WT mice exposed to mOHT, injected Hif1α cKO retinas did not show vascular complexity deficits compared to non-injected Hif1α cKO retinas.
Conclusions :
These preliminary results suggest that Hif1α is required for early vascular remodeling following mOHT. Expansion of the dataset will be necessary to confirm the findings and assess for more subtle phenotypes.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.