Progressive loss of retinal blood vessels in a live model of retinitis pigmentosa

Abstract

Objective: To assess retinal blood vessels in a live retinitis pigmentosa (RP) model with rd1 mutation and green fluorescent protein (GFP) expressed in vascular endothelium.

Methods: Homozygous (hm) Tie2-GFP mice with rd1 mutation and known retinal degeneration were crossed with wild-type CD1 mice to generate control heterozygous (ht) Tie2-GFP mice. The retinas of 16 live hm mice were evaluated at 2 weeks and 3, 5, and 8 months of age, and compared with age-matched control ht and CD1 mice by optical coherence tomography (OCT) and confocal scanning laser ophthalmoscopy (cSLO). Fluorescence intensity was measured and compared between strains at 3, 5, and 8 months. In vivo findings were validated by immunostaining with collagen IV and isolectin histopathology.

Results: All hm Tie2-GFP mice showed progressive outer retinal degeneration by OCT. Loss of small branches of blood vessels and then larger main vessels was seen by cSLO. Retinal tissue and vessels were preserved in control ht mice. At all ages, measurements of fluorescence intensity were reduced in hm compared with ht mice (p < 0.001). In all strains, intensity at 8 months was reduced compared with 3 months (p < 0.001) and 5 months (p = 0.021). Histopathological studies confirmed in vivo findings and revealed a pattern of blood vessel regression in the deep plexus, followed by intermediate and superficial retinal plexuses.

Conclusions: This is the first evidence of progressive loss of retinal blood vessels in a live mouse model of RP. These findings may be highly relevant to understanding retinal degeneration in RP to prevent blindness.