Histochemical study of retinal photoreceptors development during pre- and postnatal period and their association with retinal pigment epithelium

Document Type : Original Article


Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran


Objective(s):The aim of this study was to evaluate distribution and changes of glycoconjugates of retinal photoreceptors during both pre- and postnatal development.
Materials and Methods: Tissue sections from days 15 to 20 of Wistar rat embryos and 1 to 12 postnatal days of rat newborns including developing eye were prepared for lectinhistochemistry technique. Horseradish peroxidase (HRP)-labeled lectins including Vicia villosa (VVA), peanut agglutinin (PNA), Maclura pomifera (MPA) and wheat germ agglutinin (WGA-ІІ) were used. Alcian blue (pH 2.5) was used for counterstaining.
Results: Interphotoreceptor matrix (IPM) plays a crucial role in photoreceptors differentiation and acts as a mediator in interactions between photoreceptors and retinal pigment epithelium (RPE). Specific cell surface glycoconjugates secreted from cone cells could help us to distinguish these cells from rod photoreceptors. Our results for the first time revealed the strong reaction of cone photoreceptors with the cone-specific lectin (PNA) at postnatal day 12 (P12).  Postnatal day 12 can be determined as the final differentiation of cone photoreceptors.
Conclusion: According to our findings, we suggest that the generation of the eye photoreceptors begins from pre- natal period and their final differentiations will continue to postnatal period. Glycoconjugates including (β-D-Gal [1–3]-D-GalNac) and (β-D-Gal) terminal sugars play a critical role in the pre- and postnatal development and differentiation of retinal photoreceptors.


1. Araki M. Regeneration of the amphibian retina: role of tissue interaction and related signaling molecules on RPE transdifferentiation. Dev Growth Differ 2007; 49:109-120.
2. Hartenstein V, Reh TA. Homologies between vertebrate and invertebrate eyes.  Drosophila eye development: Springer; 2002; 37:219-255.
3. Blackshaw S, Harpavat S, Trimarchi J, Cai L, Huang H, Kuo WP, et al. Genomic analysis of mouse retinal development. PLoS Biol 2004; 2:247.
4. Nicholls JG, Martin AR, Wallace BG, Fuchs PA. From neuron to brain. Sinauer Associates Sunderland MA; 2001.
5. Burns ME, Arshavsky VY. Beyond counting photons: trials and trends in vertebrate visual transduction. Neuron 2005; 48:387-401.
6. Hyer J, Mima T, Mikawa T. FGF1 patterns the optic vesicle by directing the placement of the neural retina domain. Development 1998; 125:869-877.
7. Taranova OV, Magness ST, Fagan BM, Wu Y, Surzenko N, Hutton SR, et al. SOX2 is a dose-dependent regulator of retinal neural progenitor competence. Genes Dev 2006; 20:1187-1202.
8. Young RW. Cell differentiation in the retina of the mouse.  Anat Rec 1985; 212:199-205.
9. Hinds JW, Hinds PL. Differentiation of photoreceptors and horizontal cells in the embryonic mouse retina: an electron microscopic, serial section analysis. J Comp Neurol 1979; 187:495-511.
10. Jacobs GH, Williams GA, Fenwick JA. Influence of cone pigment coexpression on spectral sensitivity and color vision in the mouse. Vis Res 2004; 44:1615-1622.
11. Lin B, Masland RH, Strettoi E. Remodeling of cone photoreceptor cells after rod degeneration in rd mice. Exp Eye Res 2009; 88:589-599.
12. Swaroop A, Kim D, Forrest D. Transcriptional regulation of photoreceptor development and homeostasis in the mammalian retina. Nat Rev Neurosci 2010; 11:563-576.
13. Rapaport DH, Wong LL, Wood ED, Yasumura D, LaVail MM. Timing and topography of cell genesis in the rat retina. J Comp Neurol 2004; 474:304-324.
14. Turner DL, Snyder EY, Cepko CL. Lineage-independent determination of cell type in the embryonic mouse retina. Neuron 1990; 4:833-845.
15. Strauss O. The retinal pigment epithelium in visual function. Physiol Rev 2005; 85:845-881.
16. Simo R, Villarroel M, Corraliza L, Hernandez C, Garcia-Ramirez M. The retinal pigment epithelium: something more than a constituent of the blood-retinal barrier—implications for the pathogenesis of diabetic retinopathy. J Biomed Biotechnol 2010; 119-129.
17. Aramant RB, Seiler MJ. Transplanted sheets of human retina and retinal pigment epithelium develop normally in nude rats. Exp Eye Res 2002; 75:115-125.
18. Hauck SM, Schoeffmann S, Deeg CA, Gloeckner CJ, Swiatek de Lange M, Ueffing M. Proteomic analysis of the porcine interphotoreceptor matrix. Proteomics 2005; 5:3623-3636.
19. Lazarus HS, Sly WS, Kyle JW, Hageman GS. Photoreceptor degeneration and altered distribution of interphotoreceptor matrix proteoglycans in the mucopolysaccharidosis VII mouse. Exp Eye Res 1993; 56:531-541.
20. Jablonski MM, Tombran-Tink J, Mrazek DA, Iannaccone A. Pigment epithelium-derived factor supports normal development of photoreceptor neurons and opsin expression after retinal pigment epithelium removal. J Neurosci 2000; 20:7149-7157.
21. Cho E, Choi H, Chan FL. Expression pattern of glycoconjugates in rat retina as analysed by lectin histochemistry. Histochem J 2003; 34:589-600.
22. D’Souza YB, Jones CJ, Bonshek RE. Comparison of lectin binding of drusen, RPE, Bruch’s membrane, and photoreceptors. Mol Vis 2009; 15:906.
23. Fariss RN, Anderson DH, Fisher SK. Comparison of photoreceptor-specific matrix domains in the cat and monkey retinas. Exp Eye Res 1990; 51:473-485.
24. Garlipp MA, Gonzalez-Fernandez F. Cone photo-receptor and Müller cell pericellular matrices are binding domains for Interphotoreceptor Retinoid-Binding Protein (IRBP). Exp Eye Res 2013; 13:192-202.
25. Rouge P, Culerrier R, Granier C, Rance F, Barre A. Characterization of IgE-binding epitopes of peanut              (Arachis hypogaea) PNA lectin allergen cross-reacting with other structurally related legume lectins. Mol Immunol 2010; 47:2359-2366.
26. Fazel A, Thompson R, Sumida H, Schulte B. Lectin histochemistry of the embryonic heart: expression of terminal and penultimate galactose residues in developing rats and chicks. Am J Anatomy 1989; 184:85-94.
27. Ebrahimzadeh BA, Hassanzadeh TMM, Nikravesh MR, Fazel AR. Lectin histochemical study of vasculogenesis during rat pituitary morphogenesis. Iran J Basic Med Sci 2011; 14:35-41.
28. White JM. ADAMs: modulators of cell–cell and cell–matrix interactions. Curr Opin Cell Biol 2003; 15:598-606.
29. Chen SS, Fitzgerald W, Zimmerberg J, Kleinman HK, Margolis L. Cell-Cell and cell-extracellular matrix interactions regulate embryonic stem cell differentiation. Stem Cells 2007; 25:553-561.
30. Kevany BM, Palczewski K. Phagocytosis of retinal rod and cone photoreceptors. Physiology 2010; 25:8-15.
31. Ishikawa M, Fujiwara T, Yoshitomi T. Temperature-dependent ultrastructural changes in the cone interphotoreceptor matrix. Japan J Ophthalmol 2009; 53:536-540.
32. Cronin T, Raffelsberger W, Lee-Rivera I, Jaillard C, Niepon M-L, Kinzel B, et al. The disruption of the rod-
derived cone viability gene leads to photoreceptor dysfunction and susceptibility to oxidative stress. Cell Death Differ 2010; 17:1199-1210.
33. Hausman RE. Ocular extracellular matrices in development. Prog Retin Eye Res 2007; 26:162-188.