Biology subjects

Rex, T. S.

Publications and source records attributed to Rex, T. S..

3 recordsLinked to original sources

bioRxiv2026

IOP-independent treatment for neurodegeneration in glaucoma using optimized ROS-scavenging microparticles for sustained release of erythropoietin

Glaucoma is a slow-progressing neurodegenerative disease of the optic projection to the brain and a leading cause of blindness worldwide. Current treatments are targeted towards lowering intraocular pressure (IOP), the only known, modifiable risk factor; however, this strategy is ineffective in many patients. An early hallmark of glaucomatous neurodegeneration is increased reactive oxygen species (ROS), representing an alternative opportunity for intervention to halt or slow disease progression. In this work, we optimize a ROS-scavenging copolymer, poly(propylene sulfide-co-ethylene sulfide) (PPSES), for formulation of size-controlled, stabilized, antioxidant microparticles (MPs) for sustained release of the protein erythropoietin (EPO). EPO promotes biological antioxidant defense via activation of NRF2-mediated transcription of antioxidant genes. This MP system overcomes the short half-life of EPO and leverages the combined benefits of bioactive EPO with long-lasting, inherently antioxidant PPSES MPs. The lead EPO-MP formulation preserves neurons in both mouse and non-human primate models of glaucoma through suppression of oxidative stress and optic nerve degeneration. EPO-loaded PPSES MPs represent a translationally relevant therapy for long-term management of glaucoma independent of IOP.

bioengineering↗

bioRxiv2026

Rhodopsin is a tunable capacitor buffering the toxic, desensitizing retinoids of the vertebrate eye

The eye is a marvel of evolution, but visual sensitivity introduces the risk of blinding photodamage. Here we reveal that the locus of sensitivity--the visual pigment rhodopsin --moonlights as a tunable mechanism of retinal photoprotection. Independent of signaling, light activated rhodopsin (R*) serves as an overflow capacitor buffering all-trans retinal (atRAL), a toxic and desensitizing retinoid agonist that accumulates as lipofuscin--a clinical marker of macular degeneration. Across mammals, R* stability reflects binding affinity and sequestration of atRAL (capacitance), thereby mitigating phototoxicity to a degree proportional to species photodamage risk, with human R* uniquely non-protective. A mouse model of defective atRAL clearance treated with a synthetic R* of unnaturally high atRAL capacitance preserved retinal function following light damage. This gene therapy also provided supra-physiological scotopic sensitivity despite being a signal-silent receptor, shielding neighboring dark-state receptors from agonist interference during regeneration, while also enhancing the signaling of endogenous R*. While the consensus human rhodopsin is not photoprotective, during recent evolution, mutations that protect against light damage emerged in high irradiance human environments and are now significantly associated with a 38% reduced risk of blindness and low vision. Together, our findings redefine rhodopsin as a tunable light buffer that can be leveraged to enhance photoreceptor function beyond natural limits.

biochemistry↗

bioRxiv2024

Torsion-Induced Traumatic Optic Neuropathy (TITON): A Physiologically Relevant Animal Model of Traumatic Optic Neuropathy

Traumatic optic neuropathy (TON) is a common cause of irreversible blindness following head injury. TON is characterized by axon damage in the optic nerve followed by retinal ganglion cell death in the days and weeks following injury. At present, no therapeutic or surgical approach has been found to offer any benefit beyond observation alone. This is due in part to the lack of translational animal models suitable for understanding mechanisms and evaluating candidate treatments. In this study, we developed a rat model of TON in which the eye is rapidly rotated, inflicting mechanical stress on the optic nerve and leading to significant visual deficits. These functional deficits were thoroughly characterized up to one week after injury using electrophysiology and immunohistochemistry. The photopic negative response (PhNR) of the light adapted full field electroretinogram (LA ffERG) was significantly altered following injury. This correlated with increased biomarkers of retinal stress, axon disruption, and cell death. Together, this evidence suggests the utility of our model for mimicking clinically relevant TON and that the PhNR may be an early diagnostic for TON. Future studies will utilize this animal model for evaluation of candidate treatments.

bioengineering↗