Abstract
Purpose :
In the process of the retinitis pigmentosa (RP), photoreceptor (PR) cells degenerate and are no longer capable of photoelectric conversion, resulting in inability to output retinal signals. However, spontaneous oscillation (SO) of spike activity in ganglion cells (GCs) emerges in the RP retina. Since such an SO is never observed in the healthy retina, with the development of the RP, PR’s death would cause degeneration in the elements other than the PR. Pharmacological studies speculated that AII amacrine cells (AIIAC) contribute to the firing activity, however, the detailed cause has yet to be clarified. Therefore, we attempt to identify the degenerative elements of the circuit by constructing a computational model of the retinal circuit.
Methods :
The retinal network model consists of ON/OFF cone bipolar cells (ONCBs/OFFCBs), AIIACs, and ONGCs/OFFGCs, each of which was a conductance-based neuron model. Those neuron models were connected by models of ribbon or conventional synapses, and gap junctions, based on the retinal anatomy. (i) Firstly, based on the experimental evidence on wild mice, we constructed a normal retina model. (ii) Next, we applied the known conditions for pathological state to the normal retina model. (iii) Under the (ii) condition, we searched the additional conditions that can replicate the SO.
Results :
The potential mechanisms on how the oscillations generated by AIIAC in the pathological retina could trigger the firing activity of GC were suggested as follows. (i) with respect to the ON pathway, ONGCs receive excitatory inputs from ONCBs via gap junction between ONCBs and AIIACs. Since ONCB is more hyperporalized in the pathological state, low-voltage-activated Ca2+ channels are required to trigger the SO. Therefore, it was hypothesized that T-type Ca2+channels are expressed at the axon terminal of the ONCB in the pathological retina. (ii) with respect to the OFF pathway, OFFGCs are received two types of inputs: the excitatory inputs from OFFCBs that receive inhibitory inputs from AIIACs and the inhibitory inputs directly from AIIACs. Therefore, it is considered that the SO of the OFFGCs are driven by these inputs.
Conclusions :
The results suggest that different patterns of ion channel expression occur in the pathological retina. It is reported that the RP is complicated by photopsia with a high probability, and it is considered that the SO trigger the onset of photopsia.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.