Abstract
Purpose :
Myopia is a common eye disease and also a major cause of blindness. Myopia is primarily caused by excess elongation of axial length. High myopia significantly increases the risk for severe eye diseases including macular damage, retinal detachment, blindness etc. Atropine is the currently available eye drops to effectively prevent/reduce eyeball elongation leading to treat myopia and to slow down myopia progression. However, atropine can dilate pupil which not only causes photophobia, but also leads to photo-damage. Therefore, we aimed to develop better eye drops to treat myopia and slow down myopia progression in children.
Methods :
We previously identified microRNA-328 (miR-328) as a risk factor for myopia. In this study, we used both bioinformatics and in vitro studies to search for other myopia related genes which are also regulated by miR-328. We also measured miR-328 levels in myopic eyes from mono-ocular form deprivation myopia (FDM) animals. To further establish the causal relationship between miR-328 and myopia, we designed oligonucleotide anti-sense (SHJ002) to knockdown miR-328 levels. Then SHJ002 was administrated as eye drops to treat myopia in FDM animals. The safety of SHJ002 was assayed in vitro and in vivo.
Results :
miR-328 was demonstrated to directly suppress collagen1A1 and fibromoduline both of which are the components of sclera. miR-328 levels were increased in the myopic eyes isolated from mice and rabbits. On the other hand, our oligonucleotide (SHJ002) suppressed miR-328 levels in RPE cells, fibroblast cells (3T3 cell line) and neural cells (ALT cell line). Consistently, SHJ002 increased the expression of collagen1A1, fibromoduline and PAX6, which may lead to an anti-myopia effect. We also showed that SHJ002 eye drops dose dependently reduced retinal miR-328 in the mouse eyes. SHJ002 eye drops prevented further elongation or even reversed the elongated axial length when instilled to the FDM animals. Furthermore, SHJ002 eye drops were shown to be more effective than 0.1% atropine in reducing axial length in the animal studies. Toxicology studies were conducted in rats and rabbits and no adverse effects were observed. Genotoxicity studies also revealed that SHJ002 would not affect DNA or chromosomes.
Conclusions :
The compelling data indicate the potential of the novel eye drops for myopia treatment in children. A phase I clinical trial is expected to be launched soon after the approval by US FDA.
This is a 2020 ARVO Annual Meeting abstract.