Abstract
Purpose :
Non-arteritic anterior ischemic optic neuropathy (AION) leads to visual loss due to compromised blood and oxygen supply to the retina, resulting in retinal ganglion cell apoptosis and its axon degeneration. Our study investigates whether stimulating primary visual cortex CaMKII neurons can enhance synaptic plasticity in the lateral geniculate nucleus (LGN) and mitigate vision loss in an AION mouse model.
Methods :
We introduced the human M3 muscarinic receptor gene (hM3Dq), a designer receptor exclusively activated by Clozapine-N-oxide (CNO), into CaMKII neurons in the mouse primary visual cortex via adeno-associated virus (AAV9). Two weeks post-injection, we induced AION in one eye by 564nm laser stimulation after injecting Rose Bengal into the tail vein. Subsequent to the 4 days post-AION model induction, mice received treatment of daily CNO intraperitoneal injections for 14 days. We assessed retinal thickness using optical coherence tomography (OCT) and visual function through optokinetic response (OKR) tests at 0, 3-, 7-, 14-days post-AION. Synaptic plasticity was evaluated via immunostaining for pre-synaptic (Synaptophysin 1) and post-synaptic (PSD 95) proteins in the LGN 25 days post-AION induction.
Results :
After 2 weeks stereotaxic injection into V1, the mCherry reporter gene of AAV9-CaMKII-hM3Dq-mCherry expressed into V1. CNO successfully active the CaMKII positive neuron. From OCT result, 2-weeks activation of V1: CaMKII neuron protect retinal thickness from regeneration in AION eye, restore AION eye vision loss in OKR response results. significantly increase the effective synapse in contralateral LGN.
Conclusions :
Long-term stimulation of primary visual cortex protects retina regeneration, reverse visual function loss and increase synapse plasticity in visual neurocircuit in AION mouse model. V1 stimulation is a promising treatment strategy for AION, and other optic neuropathies.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.