Retinal Transplants Restore Visual Cortex Responses

Material below summarizes the article Detailed Visual Cortical Responses Generated by Retinal Sheet Transplants in Rats With Severe Retinal Degeneration, published on December 12, 2018, in JNeurosci and authored by Andrzej T. Foik, Georgina A. Lean, Leo R. Scholl, Bryce T. McLelland, Anuradha Mathur, Robert B. Aramant, Magdalene J. Seiler, and David C. Lyon.

As humans, we rely heavily on vision. Defects in the retina can have major impacts and significantly worsen quality of life. One cause of vision loss is degeneration of photoreceptors, the cells in the retina that detect light. This occurs, for example, in people with age-related macular degeneration or retinitis pigmentosa. Many approaches have aimed to slow the loss of photoreceptors and ensuing blindness, but in some cases there are no longer sufficient photoreceptors to rescue. Therefore, the only chance to bring back vision is through injection of retinal progenitor cells or transplantation of healthy retinal sheets.

The transplantation technique has been in use and studied in animals since the late 1980s and has been a major focus of the work of Magdalene Seiler and her laboratory. Their research has shown transplanted tissue can develop and integrate with the remnants of the original retina in experimental animals. Furthermore, they have demonstrated transplants restore visual responses to flashes of light in the major visual structure of the midbrain, the superior colliculus.

In these studies, however, superior colliculus neurons responded only to simplified and nonspecific visual stimuli. Whether retinal transplants could generate responses to more relevant complex visual images remained unknown. In our recent study, we addressed this question by recording from single neurons in the primary visual cortex (V1), a key structure for higher-level visual processing involved in what we commonly consider to be conscious vision.

In our study, we examined three groups of rats designated as normal (healthy), degenerated (rat model of retinal degeneration), and transplanted (rats with degeneration that received a retinal sheet transplant). Instead of with flashes of light, visual activity was evoked by elongated black and white bars shown at different orientations and moving in various directions. These visual patterns were made using computer generated sinewave gratings, a stimulus known to evoke strong visual responses from V1 neurons in normal healthy animals.

From these stimuli, we were able to compute a neuron’s ability to respond to a number of fundamental characteristics in addition to orientation and motion, including size, contrast, and rate of movement and line thickness. Our major finding was V1 neuron responses were nearly as selective in the transplanted rats as they were in normal rats. In fact, there was no statistically significant difference between the populations of neurons from the two groups. In contrast, degenerated rats that did not receive the transplant showed little to no visual responsivity.

In the transplanted rats, the transplant only covered a portion of the host retina, and responsive V1 neurons were clustered in the location of the visual field corresponding to the location of transplant. Therefore, the non-transplanted region of the retina could serve as an internal control. Accordingly, we found the number of visually responsive cells decreased with the distance from the central location of the transplanted region. These findings support and strengthen fundamentals of retinal transplantation as a method for treating retinal degeneration.

Further, these findings contribute important knowledge to the efficacy of retinal transplantation as a means for treating blindness resulting from the loss of photoreceptors. They encourage us to continue to explore and investigate vision recovery in animal models, and to strive for translation of this approach into clinical treatments.

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Detailed Visual Cortical Responses Generated by Retinal Sheet Transplants in Rats with Severe Retinal Degeneration. Andrzej T. Foik, Georgina A. Lean, Leo R. Scholl, Bryce T. McLelland, Anuradha Mathur, Robert B. Aramant, Magdalene J. Seiler, and David C. Lyon. JNeurosci Dec 2018, 38 (50) 10709–10724; DOI: 10.1523/JNEUROSCI.1279-18.2018

David Lyon, PhD
David Lyon is vice chair of the department of anatomy and neurobiology in the School of Medicine at the University of California, Irvine. His group's research focuses on the organization, plasticity, and functional role of long range neural circuits of the visual cortex.
Andrzej Foik, PhD
Andrzej Foik is a postdoctoral researcher at the University of California, Irvine. He received his master’s degree at Warsaw University and PhD degree at the Nencki Institute of Experimental Biology, in Poland. His research interests include retinal transplantation, alternating current stimulation, viral tracing, and optogenetics. His current projects use optogenetics to investigate the role of single cell types in visual processing and retinal transplantation in vision restoration in different animal models.
David Lyon
David Lyon is vice chair of the department of anatomy and neurobiology in the School of Medicine at the University of California, Irvine.

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