Inherited retinal degenerations (IRD) are a group of diseases with high genetic heterogeneity and differences in inheritance patterns, age of onset and severity of visual dysfunction. It is one of the leading causes of blindness. In recent years, gene therapy becomes a popular research area in the treatment of genetic diseases due to the rapid development of gene diagnosis technology. Several clinical trials worldwide have proved the safety and effectiveness of gene therapies in IRD. Clinical application of adeno-associated virus -mediated gene therapies for Leber congenital amaurosis and choroideremia clinical trials indicate that patients' retinal functions were improved at different levels after treatment. There are a number of other IRD clinical trials ongoing currently, which bring new possibilities to treat IRD. This article reviews the pathogenesis of IRD, gene vectors and clinical trials in IRD.
Purpose To investigate the development of embryonic stem cells (ESC)in the subretinal space． Methods ESC were cultivated in suspension for 4 days till they developed into cell aggregates,i.e.embryonic body(EB).ESC as well as EB combined with or without RA were respectively transplanted into vitreous cavity and subretina1 space in SD rats,and the subretinal transplanted eyes,transient ischemia-reperfusion injuries were made by ligating the ophthalmic artery for 40 seconds before the transplantation .The experimental eyes were enucleated for histological and immunohistochemical assays after 14～28 d. Results The EB was found to develope into photoreceptors induced by RA in the subretinal space under an ischemia-reperfusion condition，and EB transplantation without RA induction induced multiple differentiations in the subretinal space.The single injection of RA without EB induced hyperplasia of the neural retinal cells.ESC transplanted into vitreous cavity rapidly proliferated and developed into atypical hyperplastic mass. Conclusion EB derived from ESC can differentiate into photoreceptors induced by RA in the host subretinal space under an ischemia-reperfusion condition. (Chin J Ocul Fundus Dis，2000，16：213-284)
Objective To investigate the clinical characteristics of retinal degeneration (RD) with retinal holes and the therapeutic effect of argon laser therapy. Methods The data of argon laser therapy in 210 RD patients (224 eyes) with retinal holes who underwent the treatment in our department were retrospectively analyzed, which was compared with the data of argon laser therapy in 173 RD patients (198 eyes) without retinal holes. Results In RD patients with retinal holes, 89.7% of the patients were less than 60 years old (53.3% males and 46.7% females). Grid-like degeneration was found in 65.6% of the patients in whom 87.5% had the range of degeneration less than 1 quardrant. There were oval-shaped holes in 60.7% of the patients and accompanied with limited rhegmatogenous retinal detachment (LRRD) in 23.7%. Compared with RD patients without retinal holes, the ratio of patients with the age ofge;35 years, cystic degeneration, retinal lengthways small plica, and subjective symptoms was higher in RD patients with retinal holes; while the therapeutic effect of argon laser therapy on patients with LRRD was obviously less than whom without retinal holes (Plt;0.01 ). Conclusions RD with retinal holes often occurs in youth, most of whom have grid-like degeneration with the range of le;1 qua drant. The major types of retinal holes are oval-shaped degeneration without retinal detachment. There was no sex difference in RD patients with retinal holes and most of the patients have no subjective symptoms. The therapeutic effect of prophylactic argon laser therapy on RD patients with retinal holes but no retinal detachment is satisfying. (Chin J Ocul Fundus Dis, 2006, 22: 39-41)
Objective Molecular cloning of rat retinal degeneration slow(RDS)gene cDNA. Methods Using PolyA+RNA from retina of SD rat as template,a 1555bp positive cDNA band was obtained by RT-PCR and subcloned into pBluescriptⅡKS(+) vector.The cloned fragment was analyzed with restriction endonucleases and sequencing. Results It had been proved that the cloned fragment was rat RDS/peripherin cDNA.Except for the substitute of A1242G and CA1409-1411CCA,the other sequences corresponded to that reported by Begy. Conclusion Rat RDS/peripherin cDNA was obtained.Researches on function of rat RDS/peripherin gene and its role in retinal degeneration are under way. (Chin J Ocul Fundus Dis,1999,15:97-99)
Objective To observe the effect of laser photocoagulation of the peripheral retinal holes and/or degeneration in high myopia. Methods Full fundus examination for high myopic patients was made before keratorefractive surgery with binocular indirect ophthalmoscopy.Peripheral holes,degeneration and vitreous traction were found in 206 eyes of 135 patients,and all of them were treated with laser photocoagulation. Results No retinal detachment occurred after keratorefrative operation within 1 year follows up. Conclusions Retinal laser photocoagulation is an effective and safety method before keratorefractive operation for prevention of the retinal detachment in high myopia at least in short-term observation. (Chin J Ocul Fundus Dis, 1999, 15: 135-136)
Objective To investigate the degenerative changes in the inner rat retina after photic injury.Methods After 24 hour-dark adaptation, sixty Lewis rats were exposed in a ventilated green plexiglass chamber that transmitted continuous green light between 480-520 nm with an intensity of 900～1 000 lx. After 24 hour exposure, the rats stayed in darkness and were sacrificed after 1 day, 3,7 or 14 days. The neurons in the inner retina were marked by immunohisto chemical technique and observed by light and electronic microscope.Results The apoptotic photoreceptor cells were noted after photic injury. The degeneration and decreasing number of rod bipolar cells were found after 3 days; the edema of horizontal cells occurred after 1 day but ameliorated gradually; decreasing number of amacrine cells was found after 1 day; sustained edema of ganglion cells and prolifeeration of the Müller cells were found after photic injury. Pyknotic and edematous neruronal degenerations of inner retina were found in ultrastructural study.Conclusion The neurons in the inner retina as well as Müller cells are involved in the degeneration after photic injury. Different neurons manifest different patterns of degeneration.(Chin J Ocul Fundus Dis，2003，19：201-268)
ObjectiveTo determine the signal pathway of specifically expressed oncostatin M(OSM) in lens inducing retinal degeneration in transgenic mice.MethodsA sequence-truncated OSM cDNA (661 bp) of mice was linked to αA-crytallin promoter, and was micro-injected into unicellular embryo to set up the model of transgenic mice. Reversal transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of gp130/OSMRβ receptor in the retinae of OSM transgenic and non-transgenic mice. Rabbit anti-phosphorylated STAT-3 antibody was used to detect the protein expression of phosphorylated STAT-3，and mouse anti-cytochrome C antibody was used to detect the distributing of cytochrome C in retinae. ResultsExpression of gp130/OSMRβmRNA was found in retina of non-transgenic mice. At the 17.5th day in the embryonic stage, significant accumulation of the phosphorylated STAT-3 was detected in the retinal nucleolus in OSM transgenic retina. At the first day after birth, intensive staining of cytochrome C in OSM transgenic retina was found. Conclusionsspecifically expressed OSM in lens may act on gp130/OSMRβ receptor in retinae, activate STAT-3, and cause the release of cytochrome C from mitochondria, which eventually induces widespread retinal degeneration.(Chin J Ocul Fundus Dis, 2005,21:167-169)