Abstract
Purpose :
To characterize the expression of connective tissue growth factor (CTGF), an inducer of fibrosis, in eyes with age-related macular degeneration (AMD), nonproliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR).
Methods :
Immunostaining was performed on sections from formaldehyde-fixed, paraffin-embedded autopsy eyes with no AMD (Sarks stage 1; n = 4), early AMD (Sarks 3; n = 3), intermediate AMD (Sarks 4; n = 3), geographic atrophy (Sarks 5; n = 10), and exudative AMD with disciform scars (Sarks 5-6; n = 4). Immunostaining was also performed on control eyes with diabetes mellitus but no histologic DR (n = 8); eyes with NPDR (n =10); and eyes with PDR (n = 3). None of the eyes were treated with anti-VEGF agents.
Results :
The most consistent and intense staining in all eyes was in the iris dilator muscle, followed by ciliary body epithelium. Regardless of disease status, many eyes had weak staining of the nerve fiber layer in the retina's periphery. 11 of the 46 eyes had epiretinal membranes that stained strongly for CTGF.
The macular retinal pigment epithelium (RPE) was stained weakly to moderately in eyes with more advanced AMD (Sarks 4-6). Occasional fibroblasts in disciform scars had variable, mostly weak, staining. One of 4 eyes with disciform scars had prominent CTGF expression in gliosis of degenerating neurosensory retina over the scar.
In diabetic eyes, vitreous strands overlying the vitreous base had consistent and strong staining for CTGF, unlike control eyes without diabetes. Proteinaceous exudates had strong staining for CTGF. Eyes with PDR had increased expression of CTGF in the neurosensory retina, especially strong in Müller cells and areas that appeared gliotic. One of the 3 eyes with PDR had strong expression of CTGF by RPE cells. Spindle cells in preretinal neovascular membranes stained positively in 2 PDR eyes, with strong expression of CTGF in the retina.
Conclusions :
In AMD, RPE upregulation of CTGF expression was conspicuous only in advanced stages (Sarks 4-6). Epiretinal membranes in AMD and DR expressed CTGF. The vitreous of diabetic eyes had increased levels of CTGF, even before histologic evidence of retinopathy. CTGF was upregulated in Müller cells, retinal gliosis, and preretinal membranes in eyes with PDR.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.