Elovanoids Provide Novel Therapeutic Approach to Retinal Degeneration

Elovanoids, a new class of lipid mediators synthesized in retinal pigment epithelium (RPE) cells and other cells, were recently discovered by a team of investigators at the Neuroscience Center of Excellence at Louisiana State University Health Sciences Center (LSUHSC) in New Orleans, Louisiana.

Nicolas Bazan (pictured), MD, PhD, Boyd Professor at LSUHSC New Orleans and director of the center, led the discovery team.

According to the team, elovanoids are oxygenated derivatives of omega-3 very-long-chain polyunsaturated fatty acids (VLC PUFAs, n-3). In photoreceptor cells, these VLC PUFAs are synthesized from fatty acids derived from docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) with the help of an elongase enzyme. DHA is abundant in the retina and is a precursor of signaling molecules called docosanoids, which protect cells by promoting stability and equilibrium.

In contrast, elovanoids are the first chemical messenger cells released in response to cell injury caused by neurodegenerative disease processes or oxidized fats.

“Elovanoids have unique structures and enhance the expression of pro-survival proteins in cells undergoing uncompensated oxidative stress,” Bazan said.

Such stress is an early precursor of retinal and neuronal death, and retinal structures — as well as RPE cells and photoreceptors — are under this stress constantly.

The team determined the bioactivity and structure of 2 elovanoids they termed elovanoid-32 and elovanoid-34. These 2 molecules are not only potent neuroprotectors but also cell-selective and involved in a key interaction between RPE and photoreceptor cells.

In reporting their findings, the team noted the retina may need elovanoids to sustain its functional integrity and preserve vision. The discovery of elovanoids and their role in preserving vision could lead to novel therapeutic approaches to retinal degeneration.

The team also noted that mutations in the key elongase enzyme that catalyzes the biosynthesis of VLC PFUAs, including the omega-3 type, cause inherited juvenile macular degeneration in patients with the autosomal dominant form of Stargardt’s disease. This condition results in functional defects in RPE cells and photoreceptor cells as well as loss of central vision and progressive degeneration of the macula and peripheral retina.

Other mutations in this key elongase enzyme, known as elongation of VLC fatty acids-4, or ELOV4, have been linked to spinocerebellar ataxia as well as neuronal dysfunction, hyper-excitability, seizures, and neuroichthyosis — an inherited condition marked by spasticity, scaly skin, and visual impairment. Thus, the discovery of elovanoids is important not only in ophthalmology but also in neurology.

The discovery of elovanoids represents a breakthrough in scientists’ current understanding of how cells protect themselves from impending harm, Bazan noted. As such, he expects that his team’s evidence of the existence and function of elovanoids “will be transformative in medicine.”

“These findings provide major conceptual advances of broad relevance for the survival of neural as well as any other cells in the body by turning on neuroprotection using a set of molecules that mimic how the body naturally activates this protection,” Bazan said.

A report on the discovery, “Elovanoids are novel cell-specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity,” was published online this month, in Scientific Reports.

A press release regarding the study was made available.

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