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Dario Marangoni, Camasamudram Vijayasarathy, Ronald A Bush, Lisa Wei, Rong Wen, Paul A Sieving; Intravitreal CNTF transiently improves residual cone function in CNGB3−/− mouse. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):479.
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© ARVO (1962-2015); The Authors (2016-present)
A recent report indicates that intravitreal injection of CNTF protein augments cone function in CNGB3 mutant achromat dogs. This study evaluated the possible effects of CNTF on retinal cone function in CNGB3−/− mice.
Forty-two CNGB3−/− mice [postnatal day (PND) 21-38] and 18 wild-type (WT) mice (PND 30) received a unilateral intravitreal injection of 1 μl of human recombinant CNTF (hCNTF) (1mg/ml). Eighteen CNGB3−/− control mice (PND 30) received 1µl of PBS. Rod and cone function was evaluated by scotopic and photopic flash electroretinogram (ERG) at 8 (PI8) and 15 (PI15) days post-injection. Intravitreal injections of CNTF were also given to 2 groups of Sprague Dawley (SD) rats (PND 30, n=9 and n=15) to confirm previous reports that it reduced the ERG responses. For all animals, contralateral eyes served as untreated controls. Retinal pSTAT3 levels were quantified by western blot in 3 CNGB3−/− mice and 3 SD rats 2 days after CNTF injection.
At PI8, the Naka-Rushton cone b-wave intensity-response function showed a 13% increase in Vmax (p<0.001) in CNGB3−/− mice and reduction in Vmax by 10% in WT mice (p=0.007), in CNTF treated eyes. The scotopic a-wave and scotopic b-wave Vmax were both reduced by 5% (p=n.s.) in CNGB3−/− mice and ‘K’ was increased by 0.10 log unit (p<0.001). CNTF in WT mice reduced the scotopic a-wave and the scotopic b-wave Vmax by 2% (p=n.s.) and 18% (p<0.001), respectively. PBS injections in CNGB3−/− mice had no significant effect on scotopic or photopic ERG responses. At PI15 ERG analysis in CNGB3−/− mice showed no significant difference between the CNTF injected eye and the uninjected eye. SD rats showed a reduction in the scotopic a-wave and b-wave Vmax by 12% and 13-23%, respectively, in the CNTF treated eye. Photopic responses were reduced by 42% in both groups. All CNTF injected eyes had increased retinal pSTAT3 levels.
Eight days after treatment, intravitreal hCNTF protein decreased scotopic and photopic ERG responses of WT animals whereas residual cone function in CNGB3−/− mice was improved although rod responses were diminished. These changes reverted to pre-CNTF level by 15 days after the treatment. It is not clear why CNGB3−/− photopic b-wave responds differently than WT to CNTF treatment, but it suggests that augmentation occurs by a mechanism specific to CNGB3−/− cones that outweighs the action causing the decrease seen in WT.
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