Table 1.

Eye disorders associated with lipid metabolism.

Disease	Genomic mutation		Lipids families affected	Phenotype	References
Age-related macular degeneration (AMD)	genetic associations: APOE2, CETP, LIPC, CFH, ABCR, IGF1		Lipid accumulation, lipid oxidation, drusen	Reduced light sensitivity or contrast sensitivity is the primary visual complaint, while in advanced disease, visual acuity loss is the main complaint.	(Ratnapriya and Chew, 2013) (Fletcher et al., 2014) (Rivera et al., 2000) (Jun et al., 2019) (Arroba et al., 2018) (Skowronska-Krawczyk and Chao, 2019)
Bestrophinopathy	BEST1		increase in unesterified cholesterol	Abnormal accumulation of autofluorescent material within RPE cells and bilateral macular or multifocal lesions.	(Guziewicz et al., 2017)
Bietti Crystalline dystrophy	CYP4V2		High levels of triglycerides and cholesterol storage, decreased metabolism of FA precursors into n-3 PUFAs	Multiple glistening intraretinal crystals scattered over the fundus, a characteristic degeneration of the retina, and sclerosis of the choroidal vessels, ultimately resulting in progressive night blindness and constriction of the visual field.	(Li et al., 2004) (Lee et al., 2001)
Farber’s disease	ASAH1		Increased level of ceramide was found in retinas	Retinal impairment and vision loss	(Sugita et al., 1972) (Koch et al., 1996) (Yu et al., 2019)
Gaucher disease	L444P		Accumulation of glucosylsphingosine	Tapeto-retinal degeneration, pigmented retinal lesions, intra-retinal white dots and inner retinal Gaucher cells.	(Winter et al., 2019)
Macular telangiectasia 2	SPTLC1 SPTLC2 PHGDH		Elevated deoxysphingolipid levels in circulation and RPE	Gradual loss of central vision.	(Gantner et al., 2019) (Fallon et al., 2018) (Eade et al., 2021)
Niemann-Pick disease (NPD)	ASM (SMPD1)-Types A, B NPC1, NPC2-Type C		Accumulation of sphingomyelin (ceramide-phosphocholine), phospholipid, bis(monoacylglycero)phosphate (BMP), lysosphingomyelin (sphingosine phosphocholine) cholesterol, glucocerebroside, lactosylceramide, and gangliosides	Types A-cherry red macula Types B-retinal stigmata Type C- retinal axonal degeneration	(Schuchman and Desnick, 2017) (McGovern et al., 2004) (Vanier, 2015) (Havla et al., 2020)
Retinitis pigmentosa	changes in any one of more than 70 genes		Decreased retinal dolichol, hyperlipidemia or hypolipidemia, reductions in DHA, and differences in AA levels in the plasma	Night blindness and progressive vision loss. Progressive loss of rod photoreceptor cells, followed by loss of cone photoreceptor cells.	(McColl and Converse, 1995) (Ramachandra Rao et al., 2020b)
	Bassen-Kornzweig syndrome (abetalipoproteinemia: MTTP		Low cholesterol and triglyceride levels; absence of low-density lipoprotein, a deficiency in fat-soluble vitamins and essential FAs	Retinal degeneration, hearing impairment, renal cysts and hepatomegaly. Untreated individuals may develop atypical retina pigmentation that may present with progressive loss of night vision and/or color vision in adulthood. Neuromuscular findings in untreated individuals, including progressive loss of deep tendon reflexes, vibratory sense, and proprioception; muscle weakness; dysarthria; and ataxia typically manifest in the first or second decades of life.	(McColl and Converse, 1995) (Kayden, 1972)
	Batten’s disease: CLN3		Neuronal ceroid lipofuscinoses	Affects the nervous system with increasing seizures, movement disorders, altered thought processes, and cognitive decline. Childhood neuronal ceroid lipofuscinoses include vision loss but adult-onset forms of the disease typically do not.	(Lerner et al., 1995)
	Refsum’s disease: PHYH or PEX7		Deficiency in phytanic acid α-oxidation. As a result, toxic levels of phytanic acid build up in the brain, blood, and other tissues.	Night blindness, with eventual weakness in arms and legs or unsteadiness (cerebellar ataxia). Other common symptoms include a loss of sense of smell (anosmia), rough, scaly skin (ichthyosis) and after many years, deafness.	(van den Brink et al., 2003) (Jansen et al., 1997)
	RP59: Dhdds		Decreased retina dolichol levels	Night and peripheral vision loss, constriction of visual fields, and retinal degeneration	(Zelinger et al., 2011) (Ramachandra Rao et al., 2020b)
	RP26: CERKL		Decreased spgingolipids	photoreceptors neurodegeneration and progressive vision loss	(Tuson et al., 2004) (Mirra et al., 2021)
	Peroxisomal diseases (Zellweger syndrome) :	PEX1 PEX5 PEX13 PEX26	The predominant VLC-PUFAs present in Zellweger brains are penta- and hexaenoic acids, whereas a normal brain contains C32 to C38 tetra- and pentaenoic acids. Zellweger brains also contained trace amounts of C40 n-6 VLC-PUFAs, which are absent in normal brains.	Psychomotor delay, dysmorphia, neonatal seizures, retinopathy, cataracts and hearing loss.	(FitzPatrick, 1996) (Ebberink et al., 2011) (Poulos et al., 1988)
		PEX1	Elevated C26:0 lyso-PC, 18: 2 n6 and 20: 3 n6, and very low levels of 22: 6 n3, 22: 5 n3, 22: 5 n6 in retina. Elevated C26:0 and higher ratio of C24:0/C22:0 and C26:0/C22:0 in plasma	Progressive retinopathy leading to blindness.	(Argyriou et al., 2019) (Martinez, 1992)
	Usher syndrome: Usher 1B MYO7A Usher 1C USH1C Usher 1D CDH23 Usher 1F PCDH15 Usher 1G USH1G		Lower blood levels of long-chain polyunsaturated FAs (PUFAs).	Partial or total hearing loss and vision loss that worsens over time. Vision loss occurs as the light-sensing cells of the retina gradually deteriorate (RP).	(Geng et al., 2009) (Geng et al., 2009) (Maude et al., 1998) (Géléoc and El-Amraoui, 2020)
Sandhoff disease	HEXB		Deficient degradation of glycolipids, accumulation of GM2 ganglioside	The infantile forms are characterized by progressive muscular weakness, mental retardation, blindness, and death in early childhood	(Mahuran, 1999)
Smith-Lemli-Opitz syndrome (SLOS)	DHCR7		Depletion of cholesterol, abnormal accumulation of 7-dehydrocholesterol Deceased DHA in rod OS	Progressive retinal degeneration.	(Boesze-Battaglia et al., 2008) (Tulenko et al., 2006)
Stargardt-like macular dystrophy (STGD1)	ABCA4		Accumulation of bis(monoacylgylercoro)phosphate lipids, bisretinoid and lipofuscin	Juvenile macular degeneration - reduced light sensitivity or contrast sensitivity and gradual loss of central vision.	(Anderson et al., 2017) (Zhao et al., 2021) (Cideciyan et al., 2004)
Stargardt-like macular dystrophy (STGD3)	ELOVL4		Reduced levels of C28–C38 VLC-PUFAs	Juvenile macular degeneration - reduced light sensitivity or contrast sensitivity and gradual loss of central vision.	(Bernstein et al., 2001) (McMahon et al., 2007) (Zhang et al., 2001) (Agbaga et al., 2008)