Abstract
Purpose :
Retinal degeneration (RD) is one of the most common causes of blindness in the western world. Our research aims at developing an animal model which enables the optical recording of retinal ganglion cells (RGCs) activity which can significantly enhance the functional evaluation of treatment modalities aimed at vision restoration in these patients.
Methods :
The development of the novel rat model is based on a new breed in which retinal degenerated Royal College of Surgeons (RCS) rat is crossbred with the transgenic line LE-Tg(Thy1-GCaMP6f)7, which expresses the genetic calcium indicator GCaMP6f in the RGCs.
Characterization of the novel model was obtained using Optical Coherence Tomography (OCT) imaging, histology, and ERG recording at the ages of 4, 8 and 12 weeks old. Moreover, optical recordings of RGC function in response to ex-vivo subretinal electrical stimulations were performed.
Results :
OCT imaging and histological studies revealed the RD expected in the RCS breed manifested by the decrease in retinal thickness with age (number of photoreactor rows, an average of 10.7±1.2 VS 1.0±0.4 in GCaMP6f-LE and 12 weeks old GCaMP6f-RCS, p<0.0001, respectively) and formation of subretinal debris. ERG recordings demonstrated a decrease in the b-wave amplitude with time (518.2±106.8, 291±124.2 and 13.2±4.1µV at 160Cd.s/m2 in GCaMP6f-LE, 4 and 8 weeks GCaMP6f-RCS, respectively) and its absence at 12 weeks old in the GCaMP6f-RCS rat. In addition, subretinal electrical stimulation demonstrated the feasibility of the investigation of activation thresholds and the building of strength-duration curves. In agreement with the ERG recordings, the subretinal activation threshold of the 8 weeks for the 100µsec pulse was higher compared with GCaMP6f-LE (16±6.6 VS 28±15.1 µA, p=0.038) and increased consistently with maturation (p trend <0.001).
Conclusions :
This developed breed will prove to be a vital tool in the investigation of the efficacy of vision restoration strategies, such as electrical stimulation with retinal prostheses.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.