Abstract
Purpose: :
Previous studies have shown preservation of photoreceptor nuclei and temporary preservation of ERG b–waves in the RCS rat after implantation with a subretinal microphotodiode array (Pardue et al., 2005). The purpose of this work was to characterize the origin of the neuroprotection by analyzing growth factor expression.
Methods: :
Three week–old RCS rats were divided into four groups: untreated, sham operated, implanted with an inactive device, or implanted with an active device (Optobionics Corp.). Retinal function was measured with a dark–adapted ERGs series. For RNA isolation, a 2 mm diameter trephine was used to isolated retina localized to the 1.0 mm implant. The relative expression of BDNF, CNTF, FGF1, FGF2, and GDNF in treated eyes compared to unoperated eyes was measured by quantitative RT–PCR and normalized to 18S. Retinas were also collected from wild–type Long Evans rats for comparison to the RCS rat of endogenous growth factor expression.
Results: :
One week after implantation, rats receiving an active implant had ERG b–waves that were twice as large as unoperated, sham, and inactive device groups. Corresponding quantitative RT–PCR of RNA from trephine–isolated retina punches showed 2 fold higher FGF2 expression in sham, inactive device, and active device groups compared to unoperated controls, while the active device group had the highest FGF2 expression at > seven fold over unoperated controls. No consistent changes were found in BDNF, CNTF, FGF1 and GDNF across treatment groups. Growth factor expression was noticeably different in the RCS rat compared to Long Evans controls with RCS showing an eight fold increase in FGF2 levels.
Conclusions: :
These data suggest RCS rats showing preservation of retinal function following implantation are expressing higher levels of FGF2 in retinal cells localized around the implant. This increase in FGF2 expression may be directly linked to electrical stimulation from the microphotodiode array since FGF2 levels were greater in active–implanted groups than sham or inactive treatment groups. Further quantitative RT–PCR measurements are necessary to determine if FGF2 (and other growth factor) expression is elevated beyond one week after implantation.
Keywords: neuroprotection • growth factors/growth factor receptors • retina: distal (photoreceptors, horizontal cells, bipolar cells)