Ezequiel Salido, MD/PhD
Contact Information
- Address
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108 BIOMEDICAL RD
ERMA BYRD BIOMEDICAL RESEARCH CENTER (BMRC)
Room 220
Morgantown, WV 26506
Research Interests
Our laboratory explores the extracellular matrix (ECM) and its crucial role in neuroscience. Cells within our body do not exist in isolation; they continuously engage with their surroundings, acquiring nutrients, communicating with neighboring cells, and responding to the biochemical cues of the ECM. This dynamic interaction is critical for determining tissue function and maintaining cellular health.
Our primary research area is the retina, where neuronal photoreceptor cells and glial cells, such as the retinal pigment epithelium (RPE), communicate through a specialized extracellular matrix known as the Interphotoreceptor Matrix (IPM). This matrix is not just a passive structure but an active participant in retinal health and disease. Mutations in the molecular components of the IPM can lead to severe visual impairments and blinding diseases.
Areas of interest
-Synthesis and composition of the IPM:
The IPM is compounded by a mesh of molecules that are constantly synthesized and degraded. We aim to identify these molecules, understand their interactions, and determine their mechanism of matrix assembly.
Our studies are centered on two important proteins conserved across species and linked to human diseases. These proteins are known as "interphotoreceptor matrix proteoglycans 1 and 2" (IMPG1 and IMPG2). They are proteoglycans rich in glycosylation and chondroitin sulfate. Rods and cones photoreceptors synthesize these proteins in the inner segments (IS). We aim to answer several questions related to these proteins such as: How do IMPG1 and IMPG2 molecules combine to form an IMPG-matrix that surrounds the photoreceptors? Why do IMPG1 and IMPG2 require each other to develop a healthy IPM? What is the exact size and shape of the IMPG-matrix?
Immunofluorescence technique was used to detect the localization of IMPG1 and IMPG2 in the retina through confocal microscopy.
Role of the IPM in Retinal Health and Disease:
The exchange of nutrients and molecules between the photoreceptors and the RPE takes place through the IPM. Our goal is to understand the role of the IPM in the diffusion of molecules within the photoreceptors-IPM-RPE complex in health and disease. Some of our questions extend to understand if the IPM aging alters its functional properties and how the IPM contributes to the disease mechanism of blinding diseases.
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Metabolomics studies have revealed metabolic changes in the retina and RPE of mice with an affected interphotoreceptor matrix. |
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Electron microscopy revealed changes in the extracellular matrix of mutant mice. |
Therapeutics:
Mutations in IMPG1 or IMPG2 genes can cause blinding conditions such as subretinal lesions or retinitis pigmentosa. We are developing adenovirus-based gene therapies to ameliorate or cure these genetic defects. Our goal is to evaluate the efficacy of these therapies in treating IMPG-related pathologies using mouse models that reproduce the genetic defects found in humans.
In addition, we are investigating drugs targeting the IPM as a potential therapeutic for ocular diseases.
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Gene therapy workflow |
Computational Model of the IPM: Our objective is to create mathematical models that can explain the intricate fluid dynamics that occur within the IPM. These models will help us better comprehend the processes taking place inside the IPM. Additionally, we plan to simulate the movement of nutrients within the IPM and use this data to predict the mechanisms behind diseases resulting from aberrant IPM.
Differential equations are used to simulate the response of a single photoreceptor to light, using MATLAB.