Ciliary Neurotrophic Factor protects retinal pigment epithelium and photoreceptor cells in sodium iodate induced retinal degeneration model

Abstract

Purpose : Dry age-related macular degeneration is closely related with retinal pigment epithelial (RPE) cell dysfunction and photoreceptor degeneration. Sodium iodate (NaIO₃), a chemical oxidizing agent, induces patchy retinal & RPE cell loss in multiple mammalian species. NaIO₃ model has been used to test drug candidates for treating retina & RPE degeneration. Neuroprotective effect of ciliary neurotrophic factor (CNTF) has been well demonstrated in retinal ganglion cell and photoreceptor cell damage models. In this study, we evaluated the protective effect of intravitreal (IVT) administration of recombinant human CNTF (rHCNTF) in NaIO₃ model in mice.

Methods : 20mg/kg NaIO₃ was injected intraperitoneally in 8-10 week old C57BL/6J mice_. Mice received IVT injections of 1ml rHCNTF (1.5mg or 2.0mg) or control (buffer or water) in the left eye one day prior and after NaIO₃ injection. Optical Coherence Tomography (OCT) and electroretinogram (ERG) were performed at baseline and one-week post NaIO₃ injection to evaluate the retinal structural and functional changes. One-week post NaIO_3, animals were euthanized. RPE/choroid flat mount was stained with phalloidin to evaluate the damage.

Results : Seven days after NaIO₃ injection, subretinal changes and retinal thickness loss (>50um) were observed in both eyes of the control groups (buffer, water) by OCT imaging. In contrast, there were minimal subretinal and retina thickness changes (<10um loss) in rHCNTF injected eyes. ERG showed significant protection of a, b and c wave amplitudes in rHCNTF injected eyes. Interestingly, in the contralateral noninjected eyes of rHCNTF group, there was also less retinal damage by OCT and ERG evaluation. Consistent with the in vivo observations, RPE/choroid flat mounts showed more RPE cell survival, and close to normal morphology in CNTF treated eyes. Contrarily, severe damage and loss of RPE cells were found in the control eyes.

Conclusions : Intravitreal injections of rHCNTF prevented NaIO₃ induced structural & functional damages in RPE & retina. These findings demonstrate a protective role of CNTF in RPE and photoreceptor cells after oxidative stress challenge, and support CNTF as a potential therapeutic agent for the treatment of RPE and photoreceptor loss in disease.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.