
In Vivo Molecular Changes in the Retina of Patients With Multiple Sclerosis
Author(s) -
Salut Alba-Arbalat,
Magí Andorrà,
Bernardo SánchezDalmau,
Anna Camós-Carreras,
Marina DottiBoada,
Irene Pulido-Valdeolivas,
Sara Llufriú,
Yolanda Blanco,
María Sepúlveda,
Albert Sáiz,
Oscar Batet,
Iker Bilbao,
Iratxe Torre,
Ivan Amat-Roldán,
Elena H. Martínez-Lapiscina,
Pablo Villoslada
Publication year - 2021
Publication title -
investigative ophthalmology and visual science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.935
H-Index - 218
eISSN - 1552-5783
pISSN - 0146-0404
DOI - 10.1167/iovs.62.6.11
Subject(s) - neurodegeneration , glutamate receptor , multiple sclerosis , retina , excitotoxicity , nicotinamide adenine dinucleotide , flavin adenine dinucleotide , chemistry , neuroinflammation , biochemistry , medicine , biology , inflammation , neuroscience , immunology , nad+ kinase , receptor , disease , cofactor , enzyme
Purpose Raman spectroscopy allows molecular changes to be quantified in vivo from the tissues like the retina. Here we aimed to assess the metabolic changes in the retina of patients with multiple sclerosis (MS). Methods We built a Raman spectroscopy prototype by connecting a scanning laser ophthalmoscope to a spectrophotometer. We defined the spectra of 10 molecules participating on energy supply, axon biology, or synaptic damage, which have been shown to be altered in the brain of patients with MS: cytochrome C, flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NADH), N -acetyl-aspartate (NAA), excitotoxicity, glutamate, amyloid β (Aβ), τ and α-synuclein (SNCA), phosphatidyl-ethanolamine, and phosphatidyl-choline. We studied these molecules in a prospective cohort of patients with MS, either in the chronic phase or during relapses of acute optic neuritis (AON). Results Significant changes to all these molecules were associated with age in healthy individuals. There was a significant decrease in NADH and a trend toward a decrease in NAA in patients with MS, as well as an increase in Aβ compared with healthy controls. Moreover, NADH and FAD increased over time in a longitudinal analysis of patients with MS, whereas Aβ diminished. In patients with acute retinal inflammation due to AON, there was a significant increase in FAD and a decrease in SNCA in the affected retina. Moreover, glutamate levels increased in the affected eyes after a 6-month follow-up. Conclusions Alterations of molecules related to axonal degeneration are observed during neuroinflammation and show dynamic changes over time, suggesting progressive neurodegeneration.