Maturation of the human fovea: correlation of spectral-domain optical coherence tomography findings with histology.

Purpose: To correlate human foveal development visualized by spectral-domain optical coherence tomography (SDOCT) with histologic specimens.

Design: Retrospective, observational case series.

Methods: Morphology and layer thickness of retinal SDOCT images from 1 eye each of 22 premature infants, 30 term infants, 16 children, and 1 adult without macular disease were compared to light microscopic histology from comparable ages.

Foveal cone density shows a rapid postnatal maturation in the marmoset monkey.

The spatial and temporal pattern of cone packing during marmoset foveal development was explored to understand the variables involved in creating a high acuity area. Retinal ages were between fetal day (Fd) 125 and 6 years. Cone density was determined in wholemounts using a new hexagonal quantification method.

Recombinant adeno-associated virus targets passenger gene expression to cones in primate retina.

Recombinant adeno-associated virus (rAAV) is a promising vector for gene therapy of photoreceptor-based diseases. Previous studies have demonstrated that rAAV serotypes 2 and 5 can transduce both rod and cone photoreceptors in rodents and dogs, and it can target rods, but not cones in primates. Here we report that using a human cone-specific enhancer and promoter to regulate expression of a green fluorescent protein (GFP) reporter gene in an rAAV-5 vector successfully targeted expression of the reporter gene to primate cones, and the time course of GFP expression was able to be monitored in a living animal using the RetCam II digital imaging system.

Gradients of cone differentiation and FGF expression during development of the foveal depression in macaque retina.

Cones in the foveola of adult primate retina are narrower and more elongated than cones on the foveal rim, which in turn, are narrower and more elongated than those located more eccentric. This gradient of cone morphology is directly correlated with cone density and acuity. Here we investigate the hypothesis that fibroblast growth factor (FGF) signaling mediates the morphological differentiation of foveal cones--in particular, the mechanism regulating the elongation of foveal cones.

Expression of photoreceptor-specific nuclear receptor NR2E3 in rod photoreceptors of fetal human retina.

Purpose: To study the physiological function of NR2E3 and possible molecular mechanisms underlying enhanced short-wavelength cone syndrome (ESCS) pathogenesis in developing human retina, and to compare its expression to that of Neural Retina Leucine zipper (NRL), a transcription factor essential for rod differentiation.

Methods: Expression of NR2E3, a photoreceptor-specific orphan nuclear receptor, was examined in human retinas between fetal weeks (Fwk) 9 to 22 by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. Both NR2E3 and NRL expression patterns were followed by immunocytochemistry.

Distribution of short-wavelength-sensitive cones in human fetal and postnatal retina: early development of spatial order and density profiles.

We analysed spatial density and distribution of short-wavelength-sensitive photoreceptors (S-cones) in developing and adult human retinae using antibody against short-wavelength-sensitive opsin. Statistical tests indicate that before 20 weeks of gestation (WG) the S-cone mosaic is not distinguishable from a random distribution, but by 20 WG is significantly different from a random distribution in the perifoveal region, as reported previously for adult retina. Changes in spatial density during development are consistent with displacement of the photoreceptor population towards the incipient fovea so that prior to 20 WG, peak S-cone density is >1.

The role of opsin expression and apoptosis in determination of cone types in human retina.

In primates, short wavelength sensitive cones (S cones) and medium- or long-wavelength-sensitive cones (L/M cones) are two separate populations. Each cone type has a different developmental timecourse, contributes to different intra-retinal circuits, and transmits different types of information to the brain. However, in fetal human retina a significant population of cones express both S and L/M opsin (S+L/M cones), raising questions about whether S+L/M cones die or change opsin expression during development.

Expression of photoreceptor-associated molecules during human fetal eye development.

Purpose: A characteristic feature of the human retina is the early differentiation of foveal cells followed by a central to peripheral wave of maturation. This can obscure the true onset of differentiation when regions other that the fovea are sampled, or when methods based on whole retina or whole eye tissue are employed, such as reverse transcription-polymerase chain technique (RT-PCR). In order to assess the suitability of RT-PCR based approaches during human retinal development and to gain insight into the developmental progression of photoreceptor differentiation and maturation in the human, we analyzed the expression of several photoreceptor-associated genes by immunocytochemical labeling (ICC) of the foveal region as well as by RT-PCR of total RNA from whole fetal eyes from different developmental stages.

VEGF expression by ganglion cells in central retina before formation of the foveal depression in monkey retina: evidence of developmental hypoxia.

In macaque monkeys the foveal depression forms between fetal day (Fd) 105 and birth (Fd 172 of gestation). Before this, the incipient fovea is identified by a photoreceptor layer comprising cones almost exclusively, a multilayered ganglion cell layer (GCL), and a "domed" profile. Vessels are absent from the central retina until late in development, leading to the suggestion that the GCL in the incipient fovea may be transitorily hypoxic.