The effects of transient retinal detachment on cavity size and glial and neural remodeling in a mouse model of X-linked retinoschisis.
OBJECTIVE
To determine the cellular consequences of retinal detachment in retinoschisin knockout (Rs1-KO) mice, a model for retinoschisin in humans.


METHODS
Experimental retinal detachments (RDs) were induced in the right eyes of both Rs1-KO and wild-type (wt) control mice. Immunocytochemistry was performed on retinal tissue at 1, 7, or 28 days after RD with antibodies to anti-GFAP, -neurofilament, and -rod opsin to examine cellular changes after detachment. Images of the immunostained tissue were captured by laser scanning confocal microscopy. Quantitative analysis was performed to measure the number of Hoechst-stained photoreceptor nuclei and their density, number, and size of inner retinal cavities, as well as the number of subretinal glial scars.


RESULTS
Since detachments were created with balanced salt solution, by examination, all retinas had spontaneously reattached by 1 day. Cellular responses common to many photoreceptor degenerations occurred in the nondetached retinas of Rs1-KO mice, and, of importance, RD did not appear to significantly accentuate these responses. The number of schisis cavities was not changed after detachment, but their size was reduced.


CONCLUSIONS
These data indicate that large short-term RD in Rs1-KO mice, followed by a period of reattachment may cause a slight increase in photoreceptor cell death, but detachments do not accentuate the gliosis and neurite sprouting already present and may in fact reduce the size of existing retinal cavities. This finding suggests that performing subretinal injections to deliver therapeutic agents may be a viable option in the treatment of patients with retinoschisis without causing significant cellular damage to the retina.
Luna
Gabriel
G
Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106-5060, USA.
Kjellstrom
Sten
S
Verardo
Mark R
MR
Lewis
Geoffrey P
GP
Byun
Jiyun
J
Sieving
Paul A
PA
Fisher
Steven K
SK
D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000502:physiology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D016900:Neurofilament Proteins / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D055355:Opsins / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology*; D012163:Retinal Detachment / Q000378:metabolism / Q000503:physiopathology*; D041441:Retinoschisis / Q000378:metabolism / Q000503:physiopathology*
D005136:Eye Proteins; D005904:Glial Fibrillary Acidic Protein; D016900:Neurofilament Proteins; D055355:Opsins; C108726:RS1 protein, human