**5. Future directions**

IRBP deficiency in diabetes could importantly impact DR progression although the relationship between its levels and the complications in diabetes remain unclear. Previous evidence suggest that it potentially impacts DR outcomes. In addition, some retinoid analogues have shown to be beneficial in the prevention of early stage DR due to their antioxidant properties [50, 51]. IRBP has been shown to have these anti-oxidant properties against some vision cycle retinoid sub-products [18].

[4] Park SH, Park JW, Park SJ, Kim KY, Chung JW, Chun MH, Oh SJ.Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina. Diabetologia. 2003;**46**:1260-1268 [5] Lieth E, Barber AJ, Xu B, Dice C, Ratz MJ, Tanase D, Strother JM. Glial reactivity and impaired glutamate metabolism in short-term experimental diabetic retinopathy. Penn

Interphotoreceptor Retinoid-Binding Protein Implications in Diabetic Retinopathy

http://dx.doi.org/10.5772/intechopen.72835

41

[6] Carter-Dawson L, Burroughs M. Differential distribution of interphotoreceptor retinoidbinding protein (IRBP) around retinal rod and cone photoreceptors. Current Eye Research.

[7] Anderson DH, Neitz J, Saari JC, Kaska DD, Fenwick J, Jacobs GH, Fisher SK. Retinoidbinding proteins in cone-dominant retinas. Investigative Ophthalmology & Visual Science.

[8] Schneider BG, Papermaster DS, Liou GI, Fong SL, Bridges CD.Electron microscopic immunocytochemistry of interstitial retinol-binding protein in vertebrate retinas. Investigative

[9] Gonzalez-Fernandez F, Landers RA, Glazebrook PA, Fong SL, Liou GI, Lam DMK, Bridges CDB. An extracellular retinol-binding glycoprotein in the rat eye—Characterization,

[10] Fong SL, Liou GI, Landers RA, Alvarez RA, Gonzalez-Fernandez F, Glazebrook PA, Lam DMK, Bridges CDB. Characterization, localization, and biosynthesis of an interstitial retinol-binding glycoprotein in the human eye. Journal of Neurochemistry. 1984;**42**:1667-1676

[11] Porrello K, Bhat SP, Bok D. Detection of interphotoreceptor retinoid binding protein (IRBP) mRNA in human and cone-dominant squirrel retinas by in situ hybridization. Journal of

[12] Hollyfield JG, Fliesler SJ, Rayborn ME, Fong SL, Landers RA, Bridges CD. Synthesis and secretion of interstitial retinol-binding protein by the human retina. Investigative Oph-

[13] Gonzalez-Fernandez F, Landers RA, Glazebrook PA, Fong SL, Liou GI, Lam DM, Bridges CD. An extracellular retinol-binding glycoprotein in the eyes of mutant rats with retinal dystrophy: Development, localization, and biosynthesis. The Journal of Cell Biology.

[14] Qtaishat NM, Wiggert B, Pepperberg DR. Interphotoreceptor retinoid-binding protein (IRBP) promotes the release of all-trans retinol from the isolated retina following rho-

[15] Betts-Obregon BS, Gonzalez-Fernandez F, Tsin AT. Interphotoreceptor retinoid-binding protein (IRBP) promotes retinol uptake and release by rat Müller cells (rMC-1) in vitro: Implications for the cone visual cycle. Investigative Ophthalmology & Visual Science.

[16] Carlson A, Bok D. Promotion of the release of 11-cis-retinal from cultured retinal pigment epithelium by interphotoreceptor retinoid-binding protein. Biochemistry. 1992;

dopsin bleaching illumination. Experimental Eye Research. 2005;**81**:455-463

localization and biosynthesis. Neurochemistry International. 1985;**7**:533-540

State Retina Research Group. Diabetes. 1998;**47**:815-820

Ophthalmology & Visual Science. 1986;**27**:679-688

Histochemistry & Cytochemistry. 1991;**39**:171-176

thalmology & Visual Science. 1985;**26**:58-67

1989;**8**:1331-1334

1986;**27**:1015-1026

1984;**99**:2092-2098

2014;**55**:6265-6271

**31**:9056-9062

IRBP deficiency can promote the accumulation of the cytotoxic bis-retinoid A2E. This molecule has been described to be involved in the pathogenesis of age-related macular degeneration (AMD) [52, 53] and Stargardt disease [54]. A2E is known to be able to produce cytotoxicity by destabilizing membranes, generating reactive oxygen species and producing photo-oxidation [55–58]. Since A2E is a lipofuscin precursor, fundus autofluorescence can be clinically used to detect its presence [59, 60]. However, hard exudates can decrease autofluorescence interfering with the evaluation of lipofuscin [61]. It would be expected that this accumulation of lipofuscin precursors in diabetes would increase the risk for developing AMD. Many studies have shown contradictory results and this relationship has not been established [62–65]. The actual accumulation, as well as the role of A2E in diabetes complications, is unclear and require further investigation.

It is important to reveal the mechanisms responsible for decreased IRBP in diabetes and to establish its role in DR in order to establish novel approaches for the prevention of these vision threatening events.
