Protection of mouse photoreceptors by survival factors in retinal degenerations.
OBJECTIVE
To examine the protective effect of a number of survival factors on degenerating photoreceptors in mutant mice with naturally occurring inherited retinal degenerations, including retinal degeneration (rd/rd), retinal degeneration slow (rds/rds), nervous (nr/nr), and Purkinje cell degeneration (pcd/pcd), in three different forms of mutant rhodopsin transgenic mice and in light damage in albino mice.


METHODS
Various survival factors were injected intravitreally into one eye of mice at or soon after the beginning of photoreceptor degeneration, with the opposite eye serving as the control, and the eyes were examined histologically at later ages. The survival factors included brain-derived neurotrophic factor (BDNF), neurotrophin-3, neurotrophin-4, ciliary neurotrophic factor (CNTF), Axokine (a mutein of CNTF), leukemia inhibitory factor, basic fibroblast growth factor, and nerve growth factor and insulin-like growth factor II, either alone or in various combinations.


RESULTS
Photoreceptor degeneration was slowed in rd/rd and nr/nr mutant mice and in Q344ter mutant rhodopsin mice by certain forms of CNTF; the degeneration in Q344ter mice was slowed by Axokine and by leukemia inhibitory factor; and the degeneration in a few nr/nr mice was slowed by BDNF. The other agents were ineffective in these mice, and none of the agents were effective in the other mutants and other mutant rhodopsin transgenic mice. However, light damage experiments that compared agent effectiveness in albino mice versus rats suggested a significant delivery problem with the very small mouse eye, thereby making the interpretation of negative findings equivocal in mutant mice. Basic fibroblast growth factor failed to protect the mouse retina from the damaging effects of constant light, whereas it showed a strong protective effect in the rat, indicating an important species difference.


CONCLUSIONS
The slowing of degeneration in the rd/rd and Q344ter mutant mice demonstrated that intraocularly injected survival factors can protect photoreceptors from degenerating in animal models with the same or similar genetic defects as those in human inherited retinal degenerations.
LaVail
M M
MM
Department of Anatomy, University of California, San Francisco 94143-0730, USA.
Yasumura
D
D
Matthes
M T
MT
Lau-Villacorta
C
C
Unoki
K
K
Sung
C H
CH
Steinberg
R H
RH
D000818:Animals; D004338:Drug Combinations; D006133:Growth Substances / Q000494:pharmacology*; D007267:Injections; D008027:Light / Q000009:adverse effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010786:Photoreceptor Cells / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012162:Retinal Degeneration / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D014822:Vitreous Body
D004338:Drug Combinations; D006133:Growth Substances; D018696:Neuroprotective Agents