The Effect of Cyanine Dye NK-4 on Photoreceptor Degeneration in a Rat Model of Early-Stage Retinitis Pigmentosa

Abstract

The present study aimed to evaluate the effects of NK-4 on the apoptosis of photoreceptors in a rat model of retinitis pigmentosa and explore the mechanism underlying anti-apoptosis activity. The Royal College of Surgeons (RCS) rats received an intravitreous injection of NK-4 solution in the left eye and vehicle control in the right eye. Apoptosis was detected by TUNEL method in frozen sections of the eyes. The retinal tissues of the rats were dissected for RNA-seq analysis. Functional and pathway enrichment analyses of differentially expressed genes (DEGs) were performed by using Metascape and DAVID software. The expression levels of DEGs were confirmed by real-time quantitative PCR (RT-qPCR). The number of apoptotic cells decreased in the outer nuclear layer (ONL) and the thickness of the ONL was significantly thicker in the retina of NK-4-injected eyes, compared with control eyes. Five DEGs were identified by RNA-seq analysis, and Hmox1, Mt1, Atf5, Slc7a11, and Bdh2 were confirmed to be up-regulated by RT-qPCR. Functional and pathway enrichment analysis of the up-regulated genes showed that anti-apoptosis effects of NK-4 in the retina of RCS rats may be related to the pathways of metal ion homeostasis, negative regulation of neuron death, response to toxic substance, and pigment metabolic process. We found a potential mechanism of NK-4, providing a new viewpoint for the development of more therapeutic uses of NK-4 in the future.

Mechanism and ingredients prediction of Radix Salviae-Angelicae Sinensis Radix-Lycii Fructus-Rehmanniae Radix Praeparata-Ginkgo Folium for retinitis pigmentosa therapy using network pharmacology and molecular docking analysis

“…The use of antioxidants such as curcumin ( 33 ), taurododecoxycholic acid (TUDCA) ( 34 ), n-acetylcysteine ( 35 ), lutein ( 36 ), and chlorogenic acid ( 37 ) can temporarily improve vision in PR patients. Besides, a recent study suggested that genetic mutations and overload of intracellular metal ions may cause deficiency or excess of metal ions, including Fe, Cu, and Zn, disrupting retinal metal homeostasis ( 38 ). The above results are consistent with our GO enrichment results, suggesting that RALRG can exert protective effects through multiple biological functions.…”

Effect of NK-5962 on Gene Expression Profiling of Retina in a Rat Model of Retinitis Pigmentosa

“…Eight male pink-eyed RCS (Jcl-rdy/rdy, p-) rats were obtained from CLEA Japan, Inc. (Tokyo, Japan), and reared under a 12 h light/dark cycle. All intravitreal injections were performed as described previously [6]. At the age of 3 and 4 weeks, the rats were anesthetized by intraperitoneal injection of ketamine (87 mg/kg body weight, Daiichi Sankyo, Tokyo, Japan) and xylasine (13 mg/kg, Bayer Japan, Osaka, Japan), and received an intravitreal injection of 5 µL of NK-5962 solution at 8.2 µg/mL (16 µM) in the left eye, and saline (0.9% sodium chloride) as a vehicle control in the right eye, with a 30-gauge needle-attached Hamilton syringe (50 µL 1705 LT SYR; Hamilton Company, Reno, NV, USA) under a dissecting microscope.…”

“…Patients with RP experience slowly progressive loss in the peripheral visual field, finally leading to blindness in later decades [1]. Nowadays, many treatments including neurotrophic factors [2,3], antioxidants [4][5][6], retinal prostheses [7][8][9][10][11][12], and gene therapies [13] are used to rescue retinal degeneration and improve the visual function.…”