Impaired Axonal Transport and Glaucoma

Fahy, Eamonn; Chrysostomou, Vicki; Crowston, Jonathan G

doi:10.3109/02713683.2015.1037924

Cited by 41 publications

(44 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It should be noted that CWS have been documented in several astronauts following LDSF. 1,5 As these are also seen following terrestrial radiation therapy 45 their presentation in astronauts following LDSF suggests [46][47][48][49][50][51][52][53][54] the possible role of space radiation exposure. 5 NASA is attempting to tease apart the role that each of these elements may play in SANS.…”

Section: Oct and Sansmentioning

confidence: 99%

Spaceflight associated neuro-ocular syndrome (SANS) and the neuro-ophthalmologic effects of microgravity: a review and an update

Lee

Mader

Gibson³

et al. 2020

npj Microgravity

193

180

View full text Add to dashboard Cite

Prolonged microgravity exposure during long-duration spaceflight (LDSF) produces unusual physiologic and pathologic neuroophthalmic findings in astronauts. These microgravity associated findings collectively define the "Spaceflight Associated Neuroocular Syndrome" (SANS). We compare and contrast prior published work on SANS by the National Aeronautics and Space Administration's (NASA) Space Medicine Operations Division with retrospective and prospective studies from other research groups. In this manuscript, we update and review the clinical manifestations of SANS including: unilateral and bilateral optic disc edema, globe flattening, choroidal and retinal folds, hyperopic refractive error shifts, and focal areas of ischemic retina (i.e., cotton wool spots). We also discuss the knowledge gaps for in-flight and terrestrial human research including potential countermeasures for future study. We recommend that NASA and its research partners continue to study SANS in preparation for future longer duration manned space missions.npj Microgravity (2020) 6:7 ; https://doi.

show abstract

Section: Oct and Sansmentioning

confidence: 99%

Spaceflight associated neuro-ocular syndrome (SANS) and the neuro-ophthalmologic effects of microgravity: a review and an update

Lee

Mader

Gibson³

et al. 2020

npj Microgravity

193

180

View full text Add to dashboard Cite

show abstract

“…In this model, OHT results in Wallerian-like degeneration53, which culminates in RGC death2652. In fact, previous studies have shown that part of the surviving RGC population after one week of OHT exhibits impaired retrograde axonal transport, supporting evidence that not all RGCs die immediately upon impaired axonal transport2526.…”

Section: Discussionmentioning

confidence: 76%

Caffeine administration prevents retinal neuroinflammation and loss of retinal ganglion cells in an animal model of glaucoma

Madeira

Ortín-Martínez

Nadal-Nicolás

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Glaucoma is the second leading cause of blindness worldwide, being characterized by progressive optic nerve damage and loss of retinal ganglion cells (RGCs), accompanied by increased inflammatory response involving retinal microglial cells. The etiology of glaucoma is still unknown, and despite elevated intraocular pressure (IOP) being a major risk factor, the exact mechanisms responsible for RGC degeneration remain unknown. Caffeine, which is an antagonist of adenosine receptors, is the most widely consumed psychoactive drug in the world. Several evidences suggest that caffeine can attenuate the neuroinflammatory responses and afford protection upon central nervous system (CNS) injury. We took advantage of a well characterized animal model of glaucoma to investigate whether caffeine administration controls neuroinflammation and elicits neuroprotection. Caffeine or water were administered ad libitum and ocular hypertension (OHT) was induced by laser photocoagulation of the limbal veins in Sprague Dawley rats. Herein, we show that caffeine is able to partially decrease the IOP in ocular hypertensive animals. More importantly, we found that drinking caffeine prevented retinal microglia-mediated neuroinflammatory response and attenuated the loss of RGCs in animals with ocular hypertension (OHT). This study opens the possibility that caffeine or adenosine receptor antagonists might be a therapeutic option to manage RGC loss in glaucoma.

show abstract

“…Increasing evidence indicates that functional deficits in axonal transport and neuronal signaling characterize early stages of glaucoma (Crish et al, 2010;Takihara et al, 2013;Dengler-Crish et al, 2014;Chen et al, 2015;Fahy et al, 2016) similarly to early pathologies of many chronic neurodegenerative conditions (Stokin, 2005;Conforti et al, 2007;Yoshiyama et al, 2007;Adalbert et al, 2009;Brady and Morfini, 2010). Given the slow progression of glaucomatous vision loss in humans, identification of early steps in the pathology can reveal potential targets for stopping or reversing the subsequent visual deficits.…”

Section: Discussionmentioning

confidence: 99%

Persistence of intact retinal ganglion cell terminals after axonal transport loss in the DBA/2J mouse model of glaucoma

Smith

Xia

Fening

et al. 2016

J of Comparative Neurology

View full text Add to dashboard Cite

Axonal transport defects are an early pathology occurring within the retinofugal projection of the DBA/2J mouse model of glaucoma. Retinal ganglion cell (RGC) axons and terminals are detectable after transport is affected, yet little is known about the condition of these structures. We examined the ultrastructure of the glaucomatous superior colliculus (SC) using three-dimensional serial block-face scanning electron microscopy (3-D EM) to determine the distribution and morphology of retinal terminals in aged mice exhibiting varying levels of axonal transport integrity. After initial axonal transport failure, retinal terminal densities did not vary when compared to either transport-intact or control tissue. While retinal terminals lacked overt signs of neurodegeneration, transport-intact areas of glaucomatous SC exhibited larger retinal terminals and associated mitochondria. This likely indicates increased oxidative capacity and may be a compensatory response to the stressors this projection is experiencing. Areas devoid of transported tracer label showed reduced mitochondrial volumes as well as decreased active zone number and surface area, suggesting oxidative capacity and synapse strength are reduced as disease progresses, but before degeneration of the synapse. Mitochondrial volume was a strong predictor of bouton size independent of pathology. These findings indicate that RGC axons retain connectivity after losing function early in the disease process—creating an important therapeutic opportunity for protection or restoration of vision in glaucoma.

show abstract

Impaired Axonal Transport and Glaucoma

Cited by 41 publications

References 58 publications

Spaceflight associated neuro-ocular syndrome (SANS) and the neuro-ophthalmologic effects of microgravity: a review and an update

Spaceflight associated neuro-ocular syndrome (SANS) and the neuro-ophthalmologic effects of microgravity: a review and an update

Caffeine administration prevents retinal neuroinflammation and loss of retinal ganglion cells in an animal model of glaucoma

Persistence of intact retinal ganglion cell terminals after axonal transport loss in the DBA/2J mouse model of glaucoma

Contact Info

Product

Resources

About