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Ching-Kang Jason Chen, Takae Kiyama, Yu-Jiun Chen, Chai-An Mao; Onset of neuronal oscillation requires the loss of both rod and cone photoreceptors in deafferentated retinas. Invest. Ophthalmol. Vis. Sci. 2018;59(9):962.
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© ARVO (1962-2015); The Authors (2016-present)
Many retinal neurons oscillate following photoreceptor degeneration (PD) in animal models such as RhoΔCT, Rd1 and Rd10 mice with early onset photoreceptor degeneration. We determine here whether oscillation 1) results only from early onset PD that occurs when retina is still maturing and 2) requires the loss of rod or cone or both.
Mice where the nuclear respiratory factor 1 (Nrf1) gene is floxed were bred into rod- or cone-specific Cre driver background. Degree of photoreceptor degeneration was tracked by morphology and electroretinography (ERG). Retinal oscillation driven by the gap junction network between AII amacrine cells (AIIAC) and cone ON-bipolar cells (OnCB) was monitored periodically between postnatal weeks 4 and 15 by patch clamp recording of displaced Starburst amacrine cells (dSAC) identified by intrinsic membrane properties and dendritic morphology.
Rod-specific removal of the Nrf1 gene using the iCre75 mice leads to photoreceptor degeneration after retinal maturation as gross retinal morphology and scotopic and photopic ERG responses were indistinguishable between Rod-Nrf1 knockout (Rod-Nrf1 KO) and control mice at postnatal weeks 5. The decline of scotopic a-wave amplitude in Rod-Nrf1 KO mice was noticeable at 6 weeks, with complete loss found at 10 weeks. Photopic b-wave amplitude was normal between 4 and 7 weeks, started to decline at 8 weeks and was completely lost at 12 weeks. dSAC of Rod-Nrf1 KO started to oscillate at 12 weeks and not prior, suggesting that 1) rod death alone is insufficient to cause retinal oscillation and 2) either cone death or that of both rod and cone is required to trigger oscillation. We then removed the Nrf1 gene in cones using the HGRP-Cre mice and found that cone function was completely lost at 5 months of age with minimum thinning of the outer nuclear layer and that dSAC did not oscillate as rod was still present. Cone loss alone is thus also insufficient to trigger retinal oscillation.
Our data demonstrate that early onset PD that occurs concomitantly during retinal development is not the sole cause for oscillation, as it also occurs when deafferentation takes place later in life. Moreover, loss of rod or cone alone did not trigger oscillation. The oscillation of dSAC in Rod-Nrf1 KO mice, which is through the AIIAC/OnCB mechanism, occurs only when functions of both rod and cone are lost.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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