In human development, choroidal melanocytes become evident in the final trimester of development, but little else is known about them. In fact, according to available literature, the function of melanocytes in this tissue is not yet fully elucidated.1 To better understand these melanin-producing cells, and in particular their relation to the developing vasculature and immune cells, researchers examined the precursors of melanocytes, melanoblasts (MB), in mouse eyes during development.2 They found that these MBs populate the embryonic choroid prior to the development of vascular elements.2 The study was published in Investigative Ophthalmology and Visual Science.

Researchers used wholemounts and confocal microscopy to investigate the developing choroid in the eyes of naïve albino mice [E15.5 (n=2), E18.5 (n=4), P0 (n=7), P2 (n=4), P4 (n=4), P6 (n=4), and P8 (n=4)]. Adult dams (n=4) were used as controls. Antibodies against tyrosinase-related protein 2 (TRP2), ionized calcium binding adaptor molecule-1 (Iba-1), or isolectin B4 were used to stain whole eyes, posterior segments, or dissected choroidal wholemounts. Researchers used Imaris software to quantify the cell-surface area (mm²) and volume (mm³) for MB/melanocytes (TRP2+) and myeloid (Iba-1+) cell populations in the developing choroid.2

A few MB in tissue deep to the retinal pigment epithelium were found in confocal analysis of strained posterior segment wholemounts at E15.5. The cell density was significantly increased at P0 (695.2±87.1 cells/mm²; P =.032) and P6 (1248.0±156.7 cells/mm²; P <.001). There was a higher MB density at the posterior portion of the choroid closer to the optic nerve that became less evident from P0 onwards. Developing choroidal vasculature formed in the mesenchyme around the developing optic nerve as early as E15.5; MB identified at E15.5 and E18.5 were not closely associated with larger vessels. Iba-1+ myeloid cells could be identified in the developing choroid at early time points in greater densities than MB at E15.5. In later postnatal eyes, MB quickly came to outnumber the myeloid cells.2

The mouse model has been used as an analog for human development and comparisons to time points in human development can be made. Researchers found TRP2+ MB in the presumptive choroid of mice at the earliest time point of E15.5, which is comparable with 8 to 9 weeks of development in humans.2


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“These findings contradict previous reports stating that most melanosomes in choroidal melanocytes are produced postnatally,” the researchers concluded.2 “We have demonstrated that MB are present from the earliest stages of choroidal development, with a clear association with the vasculature emerging as the eye further matures. MB migrate into the choroid earlier than previously appreciated; the precise factors controlling the differentiation of [neural crest cells] into choroidal MB and [Schwann cell precursors] in the periocular mesenchyme are unknown. The previously held view that in the developing mammalian eye, melanocytes migrated into a near mature choroid is no longer tenable based on our data.”2

Reference

  1. Weidmann C, Pomerleau J, Trudel-Vandal L, Landreville S. Differential responses of choroidal melanocytes and uveal melanoma cells to low oxygen conditions. Mol Vis. 2017;23:103-115.
  2.  McMenamin PG, Shields GT, Seyed-Razavi Y, et al. Melanoblasts populate the mouse choroid earlier in development than previously describedInvest Ophthalmol Vis Sci. 2020;61(10):33. doi: 10.1167/iovs.61.10.33