Location of Retinal Pigment Epithelial Cells in the Eye Is Critical to Their Function.

The eye is an extension of the brain and a highly sophisticated sensory organ. The intricacy of the eye is well appreciated on examination of the exquisite posterior pole, composed of numerous interconnected cell and tissue types. These types broadly include the multicellular neural retina; a single layer of epithelial cells providing support to the retina, called the retinal pigment epithelium; a multilaminar extracellular matrix called the Bruch membrane; and the choroid, a thin, trilaminar connective tissue adjacent to the Bruch membrane, composed of a dense web of vessels, pigments, and immune cells. 1 Choudhary M. Malek G. Potential therapeutic targets for age-related macular degeneration: the nuclear option. Prog Retin Eye Res. 2022; 101130 PubMed Google Scholar The posterior pole can be partitioned into two regions, the macula and the periphery, adding another tier of complexity to the eye. The anatomic macula, when evaluated histologically, is an oval-shaped region approximately 5 mm in diameter, centrally located in the posterior pole of eye. Though covering approximately 4% of the retina, it is densely composed of cone photoreceptors, facilitating high-resolution color vision. The rest of the retina is rich in rod photoreceptors, involved in side, or peripheral, and night vision. Other regional differences include, but are not limited to, variances in the structural architecture of the retinal layers, cellular distribution, and blood flow. 2 Johnson M. Dabholkar A. Huang J.D. Presley J.B. Chimento M.F. Curcio C.A. Comparison of morphology of human macular and peripheral Bruch's membrane in older eyes. Curr Eye Res. 2007; 32: 791-799 Crossref PubMed Scopus (35) Google Scholar , 3 Quinn N. Csincsik L. Flynn E. Curcio C.A. Kiss S. Sadda S.R. Hogg R. Peto T. Lengyel I. The clinical relevance of visualising the peripheral retina. Prog Retin Eye Res. 2019; 68: 83-109 Crossref PubMed Scopus (70) Google Scholar , 4 Sabeti F. Lane J. Rohan E.M.F. Rai B.B. Essex R.W. McKone E. Maddess T. Correlation of central versus peripheral macular structure-function with acuity in age-related macular degeneration. Transl Vis Sci Technol. 2021; 10: 10 Crossref PubMed Scopus (9) Google Scholar Thus, it may come as no surprise that human retinal diseases demonstrate regional selectivity, in which a cell or tissue type is particularly vulnerable in one area while in adjacent zones may remain mostly unaffected. In this issue of the American Journal of Pathology, Mullin et al 5 Mullin N.K. Voigt A.P. Boese E.A. Liu X. Stone E.M. Tucker B.A. Mullins R.F. Transcriptomic and chromatin accessibility analysis of the human macular and peripheral retinal pigment epithelium at the single-cell level. Am J Pathol. 2023; Abstract Full Text Full Text PDF PubMed Google Scholar explore several essential questions in this realm: Is there region-associated heterogeneity in retinal pigment epithelial cells, whose dysfunction is central to the development of several vision-debilitating diseases?; What are the differences in the expression profiles of retinal pigment epithelial cells in the macula versus the periphery?; and Could regional differences in the levels of expression in retinal pigment epithelial cells be linked to susceptibility to disease? Transcriptomic and Chromatin Accessibility Analysis of the Human Macular and Peripheral Retinal Pigment Epithelium at the Single-Cell LevelThe American Journal of PathologyPreviewSome human retinal diseases are characterized by pathology that is restricted to specific cell types and to specific regions of the eye. Several disease entities either selectively affect or spare the macula, the retina region at the center of the posterior pole. Photoreceptor cells in the macula are involved in high-acuity vision and require metabolic support from non-neuron cell types. Some macular diseases involve the retinal pigment epithelium (RPE), an epithelial cell layer with several metabolic-support functions essential for the overlying photoreceptors. Full-Text PDF