Retinoic acid synthesis by a population of choroidal stromal cells

Summers, Jody A.; Cano, Elizabeth Martinez; Kaser-Eichberger, Alexandra; Schroedl, Falk

doi:10.1016/j.exer.2020.108252

Cited by 15 publications

(7 citation statements)

References 54 publications

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“…We observed significant increases in three subpopulations of vascular endothelial cells in recovering eyes as compared with control eyes following 24 hrs of recovery, suggesting that recovery is associated with choroidal angiogenesis. This observation is in agreement with our previous observation of an increased number of proliferating endothelial cells in recovering choroids based on BRDU incorporation (Summers, Cano et al, 2020).…”

Section: Discussionsupporting

confidence: 94%

Single Cell Transcriptomics Identifies Distinct Choroid Cell Populations Involved in Visually Guided Eye Growth

Summers

Cano

Sharp

et al. 2023

Preprint

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Postnatal ocular growth is regulated by a vision-dependent mechanism, termed 'emmetropization', which acts to minimize refractive error through coordinated growth of the ocular tissues. Many studies suggest that the ocular choroid participates in the emmetropization process via the production of scleral growth regulators that control ocular elongation and refractive development. To elucidate the role of the choroid in emmetropization, we used single-cell RNA sequencing (scRNA-seq) to characterize the cell populations in the chick choroid and compare gene expression changes in these cell populations during conditions in which the eye is undergoing emmetropization. UMAP clustering analysis identified 24 distinct cell clusters in all chick choroids. 7 clusters were identified as fibroblast subpopulations; 5 clusters represented different populations of endothelial cells; 4 clusters were CD45+ macrophages, T cells and B cells; 3 clusters were Schwann cell subpopulations; and 2 clusters were identified as melanocytes. Additionally, single populations of RBCs, plasma cells and neuronal cells were identified. Significant changes in gene expression between control and treated choroids were identified in 17 cell clusters, representing 95% of total choroidal cells. The majority of significant gene expression changes were relatively small (< 2 fold). The highest changes in gene expression were identified in a rare cell population (0.11% - 0.49% of total choroidal cells). This cell population expressed high levels of neuron-specific genes as well as several opsin genes suggestive of a rare neuronal cell population that is potentially light sensitive. Our results, for the first time, provide a comprehensive profile of the major choroidal cell types and their gene expression changes during the process of emmetropization as well as insights into the canonical pathways and upstream regulators that coordinate postnatal ocular growth.

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Section: Discussionsupporting

confidence: 94%

Single Cell Transcriptomics Identifies Distinct Choroid Cell Populations Involved in Visually Guided Eye Growth

Summers

Cano

Sharp

et al. 2023

Preprint

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“…Summers et al reported the changes of RALDH2 + cells in the choroid of the chick myopia model during the recovery stage of myopia, Frontiers in Cell and Developmental Biology frontiersin.org finding that the RALDH2 + cells existed mainly in the choroid stroma and vascular attachment, and would continue to rise during the recovery stage of myopia. The choroid would also thicken within 4 days of the recovery stage and the trend of RE, AL, and CT increasing was consistent with the change of RALDH2 (Summers et al, 2020). In addition, the phenomenon of CT enlargement in the myopic model has also been reported by Liang et al who found that the retina and choroid of chicks would thicken within 6 days of form deprivation, and then the thickness of the retina would first return to normal.…”

Section: Discussionsupporting

confidence: 81%

Effects of exogenous retinoic acid on ocular parameters in Guinea pigs with form deprivation myopia

Feng

Yang

et al. 2023

Front. Cell Dev. Biol.

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Aim: Myopia is a common chronic eye disease, this study is to investigate the effects of exogenous retinoic acid (RA) on intraocular parameters, especially choroidal thickness (CT) and retinal thickness (RT), in guinea pigs with form deprivation myopia (FDM).Methods: A total of 80 male guinea pigs were divided randomly into 4 groups: Control, FDM, FDM + RA, and FDM + Citral groups. The FDM + RA group was given 24 mg/kg RA dissolved in 0.4 mL peanut oil; the FDM + Citral group was given citral 445 mg/kg dissolved in 0.4 mL peanut oil; The other two groups were given 0.4 mL peanut oil. After 4 weeks, the refractive error (RE), axial length (AL), and intraocular pressure (IOP) of all guinea pigs were measured, and the parameters of RT and CT were obtained using enhanced depth imaging optical coherence tomography (EDI-OCT).Results: After 4 weeks, both the RE and AL in the FDM and FDM + RA groups were increased, and the RT and CT in both groups were smaller than those in the Control group (p < 0.05). Only the IOP of the right eye in the FDM + RA group increased significantly (p < 0.05). The RT of the right eye of the 4 groups was compared: Control group > FDM + Citral group > FDM group > FDM + RA group. Compared with the RT of the left eye and the right eye among the 4 groups, the RT of the right eye in the FDM and FDM + RA groups was significantly less than that in the left eye (p < 0.05). Moreover, the CT of the right eye in the Control group was greater than that in the other three groups (p < 0.0001). There was no significant difference in the CT among the FDM, FDM + RA, and FDM + Citral groups (p > 0.05). In contrast to the RT results, the CT results of the left and right eyes in the FDM + Citral group showed statistically significant differences (p < 0.05).Conclusion: RA participates in the progression of FDM as a regulatory factor. Exogenous RA can increase the RE, AL, and IOP of FDM guinea pigs, and might aggravate the retinal thinning of FDM guinea pigs. Citral can inhibit these changes, but RA might not affect the thickness of the choroid.

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“… 22 – 25 There is also a report of lymphatic markers in the choroid of human fetal eyes. 26 That the choroid may have an important role in modulating scleral remodeling during eye growth, with implications for emmetropization and myopia, 27 could also offer explanations for the recently discovered cell populations displaying retinaldehyde dehydrogenase 2 activity 28 and the report of telocyte-like cells in the suprachoroidea. 28 Apart from synthesizing all- trans -retinoic acid, 29 the choroid is also known to produce several other growth factors, including vascular endothelial growth factor 30 and basic fibroblast growth factor.…”

Section: Choroid Anatomy Innervation and Physiologymentioning

confidence: 99%

“… 26 That the choroid may have an important role in modulating scleral remodeling during eye growth, with implications for emmetropization and myopia, 27 could also offer explanations for the recently discovered cell populations displaying retinaldehyde dehydrogenase 2 activity 28 and the report of telocyte-like cells in the suprachoroidea. 28 Apart from synthesizing all- trans -retinoic acid, 29 the choroid is also known to produce several other growth factors, including vascular endothelial growth factor 30 and basic fibroblast growth factor. 31 Still, it is unknown how these factors are regulated and whether they are transformed into scleral growth signals, what the responsible “start–stop” mechanisms are, and how they interplay with other choroidal functions.…”

Section: Choroid Anatomy Innervation and Physiologymentioning

confidence: 99%

IMI—The Dynamic Choroid: New Insights, Challenges, and Potential Significance for Human Myopia

Ostrin

Harb

Nickla

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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The choroid is the richly vascular layer of the eye located between the sclera and Bruch's membrane. Early studies in animals, as well as more recent studies in humans, have demonstrated that the choroid is a dynamic, multifunctional structure, with its thickness directly and indirectly subject to modulation by a variety of physiologic and visual stimuli. In this review, the anatomy and function of the choroid are summarized and links between the choroid, eye growth regulation, and myopia, as demonstrated in animal models, discussed. Methods for quantifying choroidal thickness in the human eye and associated challenges are described, the literature examining choroidal changes in response to various visual stimuli and refractive error-related differences are summarized, and the potential implications of the latter for myopia are considered. This review also allowed for the reexamination of the hypothesis that short-term changes in choroidal thickness induced by pharmacologic, optical, or environmental stimuli are predictive of future long-term changes in axial elongation, and the speculation that short-term choroidal thickening can be used as a biomarker of treatment efficacy for myopia control therapies, with the general conclusion that current evidence is not sufficient.

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Retinoic acid synthesis by a population of choroidal stromal cells

Cited by 15 publications

References 54 publications

Single Cell Transcriptomics Identifies Distinct Choroid Cell Populations Involved in Visually Guided Eye Growth

Single Cell Transcriptomics Identifies Distinct Choroid Cell Populations Involved in Visually Guided Eye Growth

Effects of exogenous retinoic acid on ocular parameters in Guinea pigs with form deprivation myopia

IMI—The Dynamic Choroid: New Insights, Challenges, and Potential Significance for Human Myopia

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