Photoreceptor rescue after low-dose intravitreal IL-1beta injection in the RCS rat.
Photoreceptor survival in the dystrophic rat was evaluated following administration of IL-1beta at dosages much lower than those used previously for this purpose. Royal College of Surgeons rats (pink-eyed, pigmented, or non-dystrophic) received 1 microl intravitreal injections of murine recombinant IL-1beta (0.5, 2, or 5 microg ml(-1); at 3 or 4 weeks of age). Eyes were harvested 4 weeks later and outer nuclear layer profiles counted. Additional animals received intravitreal basic fibroblast growth factor (1000 microg ml(-1)), or vehicle alone. Others were treated with IL-1beta to evaluate the inflammatory response (CD45+ profiles) or visual function via opto-kinetic response. IL-1beta was associated with photoreceptor rescue that was both dose-dependent and comparable to that seen following high-dose basic fibroblast growth factor. Significant anatomical rescue relative to controls was seen in both pink-eyed and pigmented strains, although the degree and distribution varied between strains. Functional rescue was confirmed by opto-kinetic response using the pigmented strain. At 5 microg ml(-1), IL-1beta resulted in numerous CD45+ profiles within the retina and vitreous. Infiltration peaked at 48 hr and was minimal at 4 weeks, without dysplastic sequelae. IL-1beta therefore induces visually significant photoreceptor rescue in a potent, dose-dependent manner that need not entail cytoarchitectural disruption. This is consistent with the known association between injury and rescue in the rat retina. Neuroprotection may be a general, if under-appreciated, consequence of inflammatory cascade activation.
Whiteley
S J
SJ
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA.
Klassen
H
H
Coffey
P J
PJ
Young
M J
MJ
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use; D019416:Head Movements / Q000187:drug effects; D007375:Interleukin-1 / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011922:Rats, Mutant Strains; D011994:Recombinant Proteins / Q000627:therapeutic use; D012162:Retinal Degeneration / Q000473:pathology / Q000517:prevention & control*
D007375:Interleukin-1; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2