Non-viral vector for gene therapy in inherited retinal degeneration / 中华实验眼科杂志

Inherited retinal degeneration (IRD), a group of diseases often causing irreversible blindness, with multiple pathogenesis, still lacks effective treatments currently.Development of effective therapeutics is a primary research goal.Despite rapid advances in gene therapy during the past decades, the most challenging aspect of gene therapy in clinical applications for IRD is to deliver the curative molecules to achieve optimal expression levels in target cells safely.Apart from high gene transfection efficiency, there are still many limitations, such as immunogenicity, biosafety issue, etc.in the application of viral vectors, which drive the development of gene therapy based on non-viral vectors.As one of the hot research topics in non-viral vectors, encouraging progress has been made in DNA nanoparticles for IRD treatment.The polymer/DNA complex nanoparticle is compacted and encapsulated DNA via peptides, lipids, or polysaccharides.Besides, the non-viral delivery system shows cost, preparation, packaging capacity, and safety advantages, providing a promising non-viral platform for safe and effective treatment of IRD, such as retinitis pigmentosa, Stargardt disease, X-linked juvenile retinoschisis, Leber congenital amaurosis, and so on.In this article, advances in transfection efficiency, targeting ability and safety of non-viral gene therapy and its application in IRD were reviewed.

Inherited retinal degeneration in a Bengal cat / 대한수의학회지

A 2-year-old intact female Bengal cat was presented with a 6-month history of visual impairment. The cat manifested bilateral negative menace responses and dazzle reflexes and sluggish pupillary light reflexes. Bilateral fundus changes included generalized tapetal hyperreflectivity, advanced retinal vascular attenuation, and increased pallor of the optic disc. A diagnosis of bilateral retinal degeneration was made. The clinical findings suggest that the investigated Bengal cat was most likely to have an inherited retinal degeneration. Further studies of the Bengal cat breed are needed to determine the prevalence of inherited retinal degeneration in this breed in Korea.

Identification of Pathogenic Variants in the CHM Gene in Two Korean Patients With Choroideremia

Choroideremia is a rare X-linked disorder causing progressive chorioretinal atrophy. Affected patients develop night blindness with progressive peripheral vision loss and eventual blindness. Herein, we report two Korean families with choroideremia. Multimodal imaging studies showed that the probands had progressive loss of visual field with characteristic chorioretinal atrophy, while electroretinography demonstrated nearly extinguished cone and rod responses compatible with choroideremia. Sanger sequencing of all coding exons and flanking intronic regions of the CHM gene revealed a novel small deletion at a splice site (c.184_189+3delTACCAGGTA) in one patient and a deletion of the entire exon 9 in the other. This is the first report on a molecular genetic diagnosis of choroideremia in Korean individuals. Molecular diagnosis of choroideremia should be widely adopted for proper diagnosis and the development of new treatment modalities including gene therapy.

Effects of interleukin-1 receptor antagonist on photoreceptor apoptosis in inherited retinal degeneration rat / 中华实验眼科杂志

Background Inherited retinal degeneration,one of the major causes of blindness worldwide,comprises a large number of disorders characterized by a slow and progressive retinal degeneration.Interleukin-1 (IL-1)was recognized to be involved in inherited retinal degeneration.Whether IL-1 receptor antagonist (IL-1ra) can arrest retinal degeneration is worthy of investigation.Objective This study was to investigate the effects of IL-1ra on photoreceptor apoptosis in Royal College of Surgeons (RCS) rats.Methods The use of the animals complied with the Regulations for the Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission.The SPF RCS rats aged 9,15,16,25,30,35,40,50 and 60 postnatal days were collected,with 9 rats for each age group.Retinal sections were used for the TdT-mediated biotin-dUTP nick-end labeling (TUNEL) cell apoptosis assay.1 μl of IL-1ra (1.8 g/L) was intravitreally injected in the right eyes of 9 RCS rats aged 15 postnatal days and PBS was used in the same way in the fellow eyes.The injection procedure was repeated on the 20 th and 25 th day,respectively.The rats were sacrificed on the 30 th day and retinal sections were prepared for the TUNEL assay.The differences in the percentage of the positive cellular nuclei area among different ages of rats were compared by one-way ANOVA,and the differences in retinal layer thickness between IL-1ra injection group and PBS injection group were assessed by paired t test.Results Photoreceptor apoptosis appeared in 20-day-old RCS rats and progressed and peaked in 30 and 35-day-old rats and then reduced,showing a significant difference among rat of various age groups (F=28.020,P＜0.01).Images from TUNEL assay showed a weaker and less TUNEL staining in the IL-1ra injected eyes than the PBS injected eyes in 30-day-old rats.The total area and relative area of TUNEL positive nuclei were (223.052±153.092) μm2 and (2.206±1.531) ％ in the IL-1ra injected group,and those in PBS injected group were (1235.050±359.767) μm2 and (7.269± 1.624) ％,with a significant difference between them (t =4.370,t=3.250,P＜0.01).The cone and rod thickness was (15.324±9.035) μm in the IL-1ra injected group and (49.566±4.605)μm in the PBS injected group,showing a significant difference (t =22.674,P＜0.01).However,no significant difference was seen in the outer nuclear layer thickness between the two groups (t =0.268,P＞0.05).Conclusions IL-1 participates in the pathogenesis and development of inherited retinal degeneration of RCS rats.The use of IL-1ra might be a potential approach in the treatment of inherited retinal degeneration.