The Effects of Transient Retinal Detachment on Cavity Size and Glial and Neural Remodeling in a Mouse Model of X-Linked Retinoschisis

Abstract

Purpose 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.

Evaluation of tolerance to lentiviral LV-RPE65 gene therapy vector after subretinal delivery in non-human primates

“…Nonetheless, these histologic data assess that this transient reaction did not provoke a chronic modification of the glial cells often observed after retinal injuries. 49,50 Importantly, the in vivo evaluation of retinal layer thickness by serial OCT scans did not show any significant thinning of inner retinal layers, where the perivascular reaction was detected.…”

Anatomical and Gene Expression Changes in the Retinal Pigmented Epithelium Atrophy 1 (rpea1) Mouse: A Potential Model of Serous Retinal Detachment

“…Following fixation, immunocytochemistry was performed as described in detail elsewhere 17,18 and processed using primary antibodies, probes, and their corresponding secondary antibodies listed in Table 1. Slides were imaged using an Olympus FluoView 1000 laser scanning confocal microscope (Olympus, Inc., Center Valley, PA USA).…”

“…15 Thus, the rpea1 mouse may prove to be the first animal model for SRD and provide the basis for developing therapies for diseases in which that is a component. While some cases of chronic SRDs can be treated with photocoagulation or photodynamic therapy to seal “leaks” in the RPE, 17 the current standard of care in many cases of the most prevalent form of SRD, CSCR, can be described as “routine observation,” and usually the retina spontaneously reattaches with the episode of detachment resolving itself. However, even after successful reattachment of the retina and a return of vision in the 20/20 to 20/25 range, 40% of patients continue to report a variety of visual “symptoms,” and 60% report scotomas to blue light.…”

Farnesyl Transferase Inhibition for the Treatment of Tauopathies

“…Brains were then dissected and immersion fixed for 48 h at 4°C. Immunocytochemistry was carried as described elsewhere(63). Briefly, samples were rinsed 5x 5 min in phosphate buffered saline (PBS; pH 7.4) and then coronally sectioned at 100 µm using a vibratome (Leica, Lumberton, NJ).…”