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Artificial Retina

Telias Lab

Welcome to the Telias Lab

Inner Retinal Remodeling

Our lab is focused on understanding the molecular and physiological mechanisms that underlie pathological remodeling of the inner retina during and after degenerative blindness. Our goal is to improve vision in retinitis pigmentosa and age-related macular degeneration patients, by blocking or reversing remodeling.

In many blinding diseases that severely affect vision or even cause its total loss, the cells of the outer retina known as photoreceptors (rods & cones) degenerate and progressively die. The cells in the inner retina survive and remain connected to the brain, but undergo a profound transformation that causes further pathological changes, known as “remodeling”. Remodeling of retinal neurons such as retinal ganglion cells (RGCs) perturbs the ability of these cells to transmit messages to the brain, further degrading vision in patients with partial vision loss, and precluding the possibility of meaningful vision restoration in blind individuals. We have found a critical role for Retinoic Acid and its receptor-mediated gene activation in causing remodeling and demonstrated that blocking this signal reduces remodeling and rescues vision.

Our goal is to understand the cascades of molecular and cellular events downstream to the activation of the retinoic acid receptor; to find new ways of blocking it; to investigate how different RGCs react differently to remodeling; and to find diagnostic markers that can predict the timing and extent of remodeling in animal models and in patients. We are also exploring the potential contribution of RA-independent mechanism on remodeling.

Fragile X Syndrome

We conduct collaborative studies aimed at elucidating the pathophysiological changes that occur at the molecular and cellular levels in neurons differentiated from stem cells carrying the mutation for Fragile X Syndrome, the most prevalent form of inherited intellectual disability and autism. Our goal is to find human-specific mechanisms.

FXS is caused by the transcriptional silencing of the FMR1 gene, present in the X-chromosome. Lack of FMR1 expression causes all symptoms and disorders associated with FXS, including mental retardation, developmental delay, autism, epilepsy, hypersensitivity, social withdrawal and more. The fact that one single gene is responsible for all these neurological dysfunctions is truly remarkable from a biological perspective. Therefore, the study of FXS and the functions of FMR1 has the potential to shed light on basic mechanisms that allow the brain to perform complex functions such as homeostatic plasticity, information processing and circuit integration.

We study FXS using human pluripotent stem cells derived from diagnosed blastocysts following single-cell pre-implantation diagnosis. These cells are pluripotent, and can be induced to differentiate into neurons and other brain cells in-vitro, providing a constant source of human material for study. Our work has demonstrated that human FXS neurons show human-specific abnormalities, not found in the predominant model of the disease, the FXS knockout mouse. Among other things, we have demonstrated that FXS human neurons have both pre- and post-synaptic dysfunctions; that their development is impaired by abnormal expression of SOX1 and SOX9; and that they do not show any dysfunction in GSK3b-mediated pathways - all of these seem to be human-specific. Our goal is to continue this line of investigation with the goal of finding new druggable targets that will hopefully be more relevant to the treatment of FXS patients than current approaches.

Michel Telias, Ph.D.

Michel Telias, Ph.D.
Principal Investigator

Projects

Closeup photo of eye

Developing Therapeutic Strategies to Inhibit Remodeling and Improve Vision 

Photo of gel in research dish

Identifying and Characterizing Molecular Markers for Diagnosis and Treatments

Illustration of a neuron

Understanding Pathological Signal-Processing Corruption in Mouse and Human Neurons

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Publications

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Contact Us

  Telias Lab
Flaum Eye Institute
MC 2-3005
601 Elmwood Ave, Box 659
Rochester, NY 14642