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Leif Erik Johnson, Michael Larsen, Maria-Thereza Perez; Adverse Retinal Effect of Fenretinide in Association with Reduced Pigmentation. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1920.
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Fenretinide is a synthetic retinoid derivative used e.g., to treat some forms of cancer. Fenretinide reduces serum levels of retinol and can lead to night blindness, which is reversible. This compound has also been tested in patients with dry macular degeneration and geographic atrophy (GA) with positive results. The purpose of this study was to analyze the effect of fenretinide in other models of photoreceptor degeneration.
Pink-eyed Royal College of Surgeon (RCS) rats, a model of Retinitis Pigmentosa (RP), pigmented Brown Norway (BN) rats and albino Sprague Dawley (SD) rats received 20 mg/kg fenretinide intraperitoneally every second day from postnatal (PN) day 10 to PN22 and were sacrificed at PN24. Two fully pigmented mouse models of RP, the rd1 and rd2 strains, and congenic C3H mice received 20 mg/kg fenretinide daily from PN7 through PN13 (rd1) or PN22 (rd2 and C3H control). All mice were sacrificed the day after the final injection. Retinas were analyzed using hematoxylin-eosin staining and the TUNEL in situ cell-death assay.
Fenretinide did not delay photoreceptor cell death in the models of RP. On the contrary, degeneration was accelerated in treated RCS rats, with the outer nuclear layer being reduced to about half the thickness of age-matched controls. A similar deleterious effect was not observed in the pigmented rd1 and rd2 mouse models. On the other hand, fenretinide also induced an almost sevenfold increase in the number of TUNEL positive photoreceptors in albino SD rats, but did not appear to have any adverse effect on BN rats.
Fenretinide accelerated retinal degeneration in selected strains of rats with preexisting degenerative disease related to pigmentation defects. This negative effect was further compounded in the RCS rat, in which there was an exceptionally rapid thinning of the outer nuclear layer, probably because photoreceptors are particularly vulnerable in this strain due to disease-induced stress.
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