Abstract
Purpose:
Subretinal electrical stimulation (SES) from a microphotodiode array (MPA) temporarily preserves retinal function (Pardue et al., PMID:15671299) and visual function (Ciavatta et al., 2012 E-ARVO abstract 6415) in dystrophic RCS rats and upregulates fibroblast growth factor 2 (FGF2). Intravitreally administered ciliary neurotrophic factor (CNTF) protects against photoreceptor apoptosis in many retinal degeneration models including the RCS rat. This study tests the hypothesis that combined SES and intravitreal CNTF injections would result in greater retinal protective effects than either treatment alone.
Methods:
RCS rats (P21) were monocularly implanted with a subretinal MPA (n=24), or nominally active device (NA) (n=10). Controls received no surgery (C) (n=13). Seven days after surgery and weekly thereafter for 2 more weeks, rats were dark-adapted, anesthetized, and flashed with increasing luminance from a Ganzfeld dome to produce short duration (<1 ms), low intensity (~1 nA/cm2 to 100 μA/cm2) pulses from the MPA. Groups were further divided into CNTF (n=10 MPA, 6 NA, 5 C) and vehicle (n=14 MPA, 3 NA, 8 C) groups. Intravitreal injections (1.5 µl) of CNTF (20μM) or vehicle (PBS) were given immediately after flash stimulation in the implanted eye. Visual acuity was assessed by OKT at 4 weeks after implantation surgery, followed by retinal function testing with ERG two days later.
Results:
Visual acuity was significantly higher in all groups receiving CNTF, MPA or CNTF+MPA compared to control vehicle treated eyes. Visual acuity measurements in CNTF, MPA or CNTF+MPA treated eyes were not significantly different from each other, but were 30% higher than non-implanted, vehicle treated eyes. Dark adapted ERG b-wave amplitudes in both CNTF and MPA treated eyes were significantly preserved by 3 to 4 fold. However, the combination of CNTF+MPA did not significantly increase ERG amplitudes over the individual treatments.
Conclusions:
After 4 weeks of treatment, both MPA and CNTF preserved visual acuity and retinal function compared to NA or vehicle treatment. However, MPA+CNTF co-treatment does not appear to be additive or synergistic. This may be due to a maximal protective effect that can be elicited by growth factors in this model.
Keywords: 543 growth factors/growth factor receptors •
510 electroretinography: non-clinical •
754 visual acuity