Research
I am a visual neuroscientist committed to preventing ocular neurodegenerative diseases that are multifactorial and enigmatic even after decades of research. I have focused my career on precision medicine directed translational research and preclinical human models.
My major research contributions to date include developing better tools to study ocular pressure, performing genetic correction of mutations, generating patient-specific retinal neurons, and identifying therapies to promote retinal neuron survival.
"The true laboratory is the mind, where behind illusions we uncover the laws of truth"
Jagadish Chandra Bose
Glaucoma and spaceflight-associated neuro-ocular syndrome are characterized by pressure-induced neurodegeneration, leading to progressive optic nerve damage and vision loss. Understanding the underlying mechanisms of pressure-related pathogenesis is critical for developing effective therapeutic strategies.
To develop effective treatments for glaucoma, my research focuses on evaluating a novel therapeutic approach aimed at preserving retinal ganglion cells (RGCs) from neurodegenerative damage. RGC degeneration is driven by trophic factor deprivation, inflammation, and activation of apoptotic pathways. One key gene implicated in neuronal plasticity and neuroprotection is Neuritin 1 (NRN1), which may play a critical role in mitigating RGC loss. We aim to explore the potential of NRN1-based interventions to enhance neuronal resilience and promote retinal cell survival in glaucoma.
To target this unique gap in knowledge, we developed the Translaminar Autonomous System, a biologically relevant preclinical system that accurately mimics pressure-induced neurodegenerative changes in the human eye. This model serves as a platform for investigating disease mechanisms, identifying biomarkers, and evaluating novel interventions for ocular pressure-related neurodegeneration. Through this research, we aim to advance therapeutic development and improve clinical outcomes for patients affected by glaucoma, SANS, and related neurodegenerative disorders.
Dr. Sharma is depicted in her laboratory setting up the perfusion system for a new human eye pressure model developed to keep post-mortem eyes alive in culture. This technology could eventually help us understand ocular disease pathogenesis as observed in glaucoma, test therapies pre-clinically in a human model system, and study their effectiveness for clinical trials.
Identifying effective cell-based therapeutic strategies to mitigate glaucomatous neurodegeneration is a critical public health priority. Previous studies have classified retinal ganglion cells (RGCs) into over 30 distinct human subtypes based on molecular markers. To investigate glaucomatous RGC subtype vulnerability, we analyzed post-mortem retinal tissues from both non-glaucomatous and glaucomatous human donor eyes. Our findings revealed significant dysregulation of RGC subtype-specific markers . These observations raise key questions regarding RGC subtype resilience—specifically, whether certain subtypes are more resistant in the central retina compared to the periphery and whether increased cell loss in the periphery is driven by subtype-specific susceptibility or simply the regional distribution of RGCs. We aim to target a critical gap in understanding the selective vulnerability of RGCs in disease progression.
Understanding the impact and severity of vision impairment during long-duration crewed Mars missions is a high-priority research area for NASA, given the potential consequences for astronaut health and mission success. Despite growing awareness of spaceflight-induced vision changes, significant knowledge gaps remain regarding the underlying mechanisms driving these alterations in the human eye.
Our future research aims to address these gaps through a conceptually innovative approach that leverages human analog models to simulate spaceflight stressors. This strategy will enable the identification of causative factors contributing to vision loss, their effects on human retinal cells, and the development of targeted countermeasures for long-duration space missions. Notably, no other research group has systematically utilized human ocular model systems to investigate the combined effects of low- and high-energy radiation and microgravity on the eye.
Building on our prior work, which examined the effects of spaceflight-associated neuro-ocular syndrome in ex vivo human eyes, we have identified oxidative stress as a key pathogenic factor. This research will provide critical insights into spaceflight-induced ocular neurodegeneration and inform the development of effective countermeasures to protect astronaut vision during extended space missions.