Future File highlights new and innovative early-stage and preclinical concepts that could one day help to advance the everyday practice of retina specialists.

Microglia Play Protective Role in Retinal Detachment

■ A research team at Massachusetts Eye and Ear has shown that microglia, the primary immune cells of the brain and retina, play a protective role in response to retinal detachment. In a report published in the journal Proceedings of the National Academy of Sciences (PNAS), the researchers describe, for the first time, the beneficial role of microglial cells in the eye after retinal detachment — migrating to the site of injury to protect photoreceptors and to regulate local inflammation.

In the PNAS report, the researchers describe morphological changes in microglia in response to retinal detachment in a preclinical model. In response to retinal detachment, microglia rapidly responded in a uniform migrating pattern, toward the affected area. When the researchers depleted microglia in the model, they saw more of the photoreceptor cells die away.

“This could prevent the initial photoreceptor cell loss, preserving vision longer after retinal detachment and providing an extended therapeutic window for surgery,” said Yoko Okuniki, MD, PhD, the study’s lead author.

Can Canine Gene Therapy Be Effective in Humans?

■ A Michigan State University veterinary ophthalmologist has modified a gene therapy that reverses blindness in dogs that have a form of a disease known as progressive retinal atrophy, or PRA, and is now looking to advance the treatment for human use. In an earlier study, the treatment on dogs had a 100% success rate in helping them restore their night vision, as well as stop them from losing their daytime vision. The progressive disease, which is similar to a disease in humans, often leads to night blindness, followed by a loss of peripheral vision and eventually total blindness.

Simon Petersen-Jones in the College of Veterinary Medicine has received a 5-year, $8.2 million grant from the National Institutes of Health to further the therapy for people who have a type of retinitis pigmentosa. PRA is an inherited condition in dogs that results from the same genes that cause RP.

Petersen-Jones and his team were the first to show that some dogs with PRA have a mutation involving a gene called cyclic nucleotide-gated channel b 1, or CNGB1, which also causes a form of RP in humans. Their approach, which was based on a gene therapy that’s been used to treat other inherited retinal degenerations, introduced a normal copy of the CNGB1 gene into the retina of affected dogs, restoring normal function and vision.

Lab-on-a-Chip Screens Retinal Drugs for Efficacy

■ Houston Methodist Research Institute has developed a new lab-on-a-chip technology that could quickly screen possible drugs to repair damaged neuron and retinal connections, like what is seen in people with macular degeneration or who have had too much exposure to the glare of electronic screens.

In a recent issue of Science Advances, researchers led by Houston Methodist nanomedicine faculty member Lidong Qin, PhD, explain how they created a sophisticated retina cell network on a chip that is modeled after a human’s neural network. They say this will further the quest for finding the right drug to treat such retinal diseases.

The NN-Chip is an improvement on Qin’s BloC-Printing Technology, which allowed researchers to print living cells onto any surface in any shape within the confines of a mold. With this latest iteration, Dr. Qin’s lab loaded and tested cells with microneedles in an open dish so researchers could tailor the neural network device, study individual cells as well as the progression of drugs through the platform’s many channels. Dr. Qin hopes the platform will have additional applications in creating models for Huntington and Alzheimer diseases and screening therapeutic drugs.

Therapeutic Inhibition of Atypical Protein Kinase C

■ Increased permeability of retinal blood vessels contributes to macular edema and the pathophysiology of many ocular diseases. Vascular endothelial growth factor induces retinal permeability and macular thickening in these diseases. Moreover, inflammatory agents, such as tumor necrosis factor-α (TNF-α), also may drive vascular permeability, specifically in poor responders to anti-VEGF therapy.

Recent evidence suggests VEGF and TNF-α induce permeability of retinal blood vessels through distinct mechanisms; however, both require the activation of atypical protein kinase C (aPKC). A recent study in The American Journal of Pathology by researchers at the Kellogg Eye Center, University of Michigan, provides evidence, using genetic mouse models and therapeutic intervention with small molecules, that inhibition of aPKC prevented or reduced vascular permeability in animal models of retinal inflammation. Expression of a kinase-dead aPKC transgene, driven by a vascular and hematopoietic restricted promoter, reduced retinal vascular permeability in an ischemia-reperfusion model of retinal injury. The data suggest that aPKC may be an attractive target for therapeutic intervention. RP