Effects of light exposure on animal models of retinal degeneration
| Gene product (symbol) | Mutation | Species | Findings* | Human counterpart† | |||||
|---|---|---|---|---|---|---|---|---|---|
| ADRP, autosomal dominant retinitis pigmentosa; ARRP, autosomal recessive retinitis pigmentosa; DR, dark rearing; LCA, Leber congenital amaurosis; NCL, neuronal ceroid lipofuscinosis; PPCA, pigmented paravenous chorioretinal atrophy; RP12, retinitis pigmentosa type 12; RPCEV, retinitis pigmentosa with Coats-like exudative vasculopathy; tg, transgenic; vLINCL, Turkish variant late infantile neuronal ceroid lipofuscinosis. | |||||||||
| *“Protection” does not necessarily imply complete rescue. Light exposure protocols vary among studies, but “exacerbation by light” refers to accelerated degeneration in light brighter than that used for routine animal housing in a given study. Because sufficiently bright light can cause retinal damage in wild type animals,6 only cases in which exacerbation of degeneration significantly exceeds the damage produced in wild type controls by the same light regimen are included. | |||||||||
| †Except where noted, the listed human diseases arise from mutations in genes orthologous to those mutated in the respective animal models. Phenotypes may not correspond precisely. Where more than one human disease is listed, these represent alternative phenotypes arising from mutations in the same gene. | |||||||||
| ‡These phenotypes are associated with mutations in the human gene TULP1 (Tubby-like protein 1), which is related to mouse Tub, but not orthologous. | |||||||||
| §Ser334ter transgenic rats exhibit dominant retinal degeneration, but this mutation has not been reported in human RP. | |||||||||
| Modified by light | |||||||||
| Arrestin (Sag) | Knockout8 | Mouse | Protection by DR9 | Oguchi disease,11 ARRP12 | |||||
| Exacerbation by light9,10 | |||||||||
| ATP/GTP binding protein 1 (Agtpbp1, Nna1) | Putative regulatory mutation (pcd1J)13 | Mouse | Exacerbation by light14 | Unknown | |||||
| Crumbs homologue 1 (Crb1) | Knockout15 | Mouse | Exacerbation by light15 | LCA, RP12, RPCEV,16 PPCA17 | |||||
| Mertk (Mertk) | Deletion18 | Rat | Protection by DR19–21 | ARRP24 | |||||
| Exacerbation by light21–23 | |||||||||
| Rds/peripherin (Rds) | Insertion25 | Mouse | No protection by DR26Exacerbation by light26 | Several forms of retinal dystrophy27 | |||||
| Rhodopsin (RHO) | Thr4Arg (T4R)28 | Dog | Exacerbation by light29 | ADRP30,31 | |||||
| Rhodopsin (Rho) | Val20Gly, Pro23His, Pro27Leu (VPP)32 | Mouse (tg) | Protection by DR33 Exacerbation by light34 | ADRP35 | |||||
| Rhodopsin (Rho) | Pro23His (P23H)36,37 | Rat (tg) | Protection by DR38 Exacerbation by light38–42 | ADRP35 | |||||
| Rhodopsin kinase (Grk1, Rhok) | Knockout43 | Mouse | Protection by DR43 Exacerbation by light10,43 | Oguchi disease44 | |||||
| Rim protein (Abca4, Abcr) | Knockout45 | Mouse | Prevention of A2E accumulation by DR46 | Stargardt disease and other retinal dystrophies47 | |||||
| RPE65 (Rpe65) | Knockout48 | Mouse | Protection by DR49 Resistance to light damage50 | LCA, early onset severe retinal dystrophy51 | |||||
| Solute carrier family 6, taurine transporter (Slc6a6, Taut) | Knockout52 | Mouse | Protection by DR53 | Unknown | |||||
| Tubby (Tub) | Splice donor site mutation54,55 | Mouse | Protection by DR56 | ARRP,57,58 LCA59‡ | |||||
| Unknown | Nervous mutation (nr)60 | Mouse | No protection by DR61 Exacerbation by light14 | Unknown | |||||
| Not modified by light | |||||||||
| Ceroid lipofuscinosis, neuronal 8 (Cln8) | Frameshift62 | Mouse | No protection by DR63 | NCL-8,62 vLINCL64 | |||||
| Microphthalmia associated transcription factor (Mitf) | Asp222Asn (D222N)65 | Mouse | No protection by DR66 | Waardenburg syndrome type II,67 Tietz syndrome68 | |||||
| Rhodopsin (Rho) | Lys296Glu (K296E)69 | Mouse (tg) | No protection by DR69 | ADRP70 | |||||
| Rhodopsin (Rho) | Ser334ter71 | Rat (tg) | No protection by DR38,72 | ADRP§ | |||||
| No exacerbation by light in most experiments38,41,73 | |||||||||
| Rhodopsin (Rho) | Knockout74 | Mouse | Resistance to light damage50 | ARRP75 | |||||