Abstract
Purpose :
Complement levels have been shown to be elevated within the vitreous of patients with Age-related macular degeneration (AMD). It remains unclear whether these elevated levels are an aspect of the disease or a response to it. Regardless, the increased complement levels are a sign of inflammation which leads to tissue damage. We hypothesize a polyacrylonitrile (PAN) based intravitreal implant, with a high affinity for complement, will decrease intraocular complement levels and attenuate complement mediated retinal damage.
Methods :
Three Complement factor h knockout mice (N=6 eyes), which have previously been shown to have elevated intraocular complement levels, as well as photoreceptor atrophy and declining retinal function, were used as a model for our study. Right eyes (N=3) were given intravitreal PAN injections, and the left eyes (N=3) were used as controls. Serial ERGs were performed on both eyes over the course of two years. Eyes were then enucleated and were prepared for H&E histology. Image Pro was used to analyze cell counts for changes in retinal morphology. A two-tailed Student’s t-test was used for statistical analysis.
Results :
ERGs showed significant (p<0.05) loss of a-wave and b-wave amplitude in sham implant and age-matched controls when compared to PAN implanted eyes. H&E histology cell counts demonstrated a significant difference between the control group and the PAN treatment group outer nuclear layer (ONL) (p<0.05) and ganglion cell layers (GCL) (p<0.05) with the control group displaying significant atrophy in the both the ONL and GCL.
Conclusions :
PAN implants preserved retinal function and morphology with attenuated photoreceptor atrophy. These findings suggest complement mediated retinal damage as a feature of disease pathology. This novel treatment may offer a therapeutic option for complement driven diseases such as AMD and diabetic retinopathy.
This is a 2020 ARVO Annual Meeting abstract.