Abstract
Purpose :
The relationship between systemic hypertension (HT) and the incidence of glaucoma, as well as the underlying mechanism responsible for the HT-induced ocular changes, remain elusive. In this study, we investigated the longitudinal changes of intraocular pressure (IOP) profile and functional retinal responses at different stages of HT.
Methods :
Stroke-prone spontaneously hypertensive rats (SHR) were used as the animal model of primary hypertension. Wistar-Kyoto rats (WKY) were used as the normotensive control animals. Measurements of IOP and functional retinal response were conducted by a rebound tonometer and full-field electroretinogram (ERG), respectively. Longitudinal monitoring of blood pressure (BP), IOP and ERG response were conducted at 4, 8, and 12 months for both species. Retinas of 12-month SHR and WKY were collected for qPCR and RNA-sequencing studies.
Results :
Systolic BP was substantially higher in SHR compared to the age matched WKY at all time points measured (N=9 for SHR, N=9 for WKY, two-way ANOVA with Bonferroni's multiple comparisons test, P<0.0001). However, IOP was consistently lower in SHR compared to WKY at all time points (9.1±0.1 mmHg in SHR vs 10.6±0.1 mmHg in WKY at 4 months; 9.2±0.1 mmHg in SHR vs 10.5±0.2 mmHg in WKY at 8 months; 9.0±0.1 mmHg in SHR vs 10.6±0.2 mmHg in WKY at 12 months, P<0.0001). Using full-field ERG, no significant differences in positive scotopic threshold response (pSTR), photopic a- and b-wave were observed at 4 months. At 8 months, SHR demonstrated a 27% reduction in the amplitude of pSTR (P<0.0001) and a 19% reduction in the amplitude of a-wave (P<0.01) compared with WKY. At 12 months, the amplitudes of pSTR, a-wave, and b-wave in SHR reduced by 40% (P<0.0001), 29% (P<0.0001), and 23% (P<0.001), respectively. The qPCR analysis revealed increased expressions of Il-1β, Cd68 and Ccl2 in the retina of 12-month SHR compared with age matched WKY, while only CD68 was found to be elevated at 8 months. The RNA-sequencing findings also demonstrated increased inflammation, complement activation, and Toll-like receptor activation in the retina of 12-month SHR compared with age-matched WKY.
Conclusions :
Chronic HT leads to progressively declined retinal functions. The reduction of functional responses from retinal ganglion cells and other retinal cells in SHR are triggered through IOP-independent, neuroinflammation-mediated mechanisms.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.