Abstract
Purpose :
Performance and development of the retinal vasculature depend on the function of mural cells (MCs). The team of authors has previously shown that the transcription factor SRF controls the expression of muscle contraction and motility genes in this context (Circ Res 22;131:308-327). Here, we focus on the effect of SRF deficiency of MC on the vascular bed of the murine retina and the associated alteration of retinal function.
Methods :
Mice that carry a MC-specific deletion of SRF (SrfiMCKO) (n=14) were used in this study and compared to control mice on a C57BL/6 genetic background (n=10). Retinal vasculature and morphology were analyzed in vivo via scanning laser ophthalmoscopy (SLO), indocyanine green (ICG) (50 mg/kg body weight) and fluorescein (FLA) (75 mg/kg bodyweight) angiography, and optical coherence tomography (OCT). Retinal function was evaluated with scotopic and photopic full-field electroretinography (ERG). One-tailed two-sample student’s t-tests assuming unequal variances were used in statistical analyses.
Results :
Retinal blood vessels of 4-week old SrfiMCKO mice exhibited vascular bulging of different degrees, which correlated well with functional ERG data. In severe cases, indicated by the presence of peripheral arteriovenous anastomoses, retinal hypoxia led to negative ERGs (b/a-wave ratio 0.69, 25%-75% quantile range=0.68,0.83) in comparison to the control group (1.65, 25%-75% quantile range=1.59,1.76, p=0.003). The most serious outcome was a partial retinal detachment observed in an 8-week old SrfiMCKO mouse, together with strongly reduced ERG responses. Interestingly, there were quite often remarkable interocular differences in the phenotype of the same individual animal.
Conclusions :
SRF deficiency in mural cells of the retinal vessels due to the SrfiMCKO mutation leads to a loss of the vascular tone regulation by smooth muscle cells, particularly affecting the arterial side. The resulting irregular pressure and blood flow eventually induces retinal ischemia indicated by a negative ERG. With increasing severity, we found vascular bulging, the formation of arteriovenous anastomoses, and ultimately a retinal detachment. The high frequency of interocular differences in the phenotype of individual SrfiMCKO mice indicates that these are rather secondary developments dependent on the local retinal context.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.