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Revealing the Mystery of RPE Thickness

Study explores RPE thickness and its link to pigmentation and genetics.

Thomas Julian, Tomas Fitzgerald, Ewan Birney, Panagiotis I. Sergouniotis

― 6 min read


RPE Thickness and RPE Thickness and Pigmentation Uncovered health and pigmentation genetics. New insights reveal links between eye
Table of Contents

The Retinal Pigment Epithelium (RPE) is a thin layer of cells found in the eye. It's located between the light-sensing photoreceptors and the deeper blood supply layer, called the choroid. The RPE has many important jobs that help keep our eyes healthy, including cleaning up after damaged cells and making sure that the visual cycle runs smoothly. It also protects the eye from harmful substances. RPE cells have a special pigment called Melanin, which is what allows them to perform these tasks effectively.

Unique Characteristics of RPE Melanin

The melanin in the RPE is different from that found in the skin and other body parts. While skin melanin is made by cells called melanocytes, the RPE creates its own melanin within its cells. This pigment is crucial for the health of the retina and usually develops early during pregnancy. Unlike other pigmented areas where melanin is produced throughout life, the RPE mainly makes melanin before and shortly after birth.

Optical Coherence Tomography (OCT) and Its Importance

Optical coherence tomography (OCT) is a fancy way of taking detailed images of the eye. It lets doctors see the different layers of the retina with high precision-about 1 to 3 micrometers. By using light waves, OCT builds a picture of the eye's structure, revealing how thick the RPE is and how much melanin it contains. The presence of melanin in the RPE affects the images produced by OCT. If there's a lot of melanin, it can reflect light differently, making it harder for the scanner to show some underlying details.

In animal studies, like those done on zebrafish, researchers found that the amount of melanin in the RPE can change the appearance and thickness of the images taken with OCT. Because the RPE is just one layer thick, its actual thickness might be influenced by both the size of the cells and how much pigment is present. Furthermore, the shape of RPE cells varies depending on where they are in the retina. Central RPE cells tend to be taller and thinner, while those further out in the retina are usually wider and flatter.

Impact of Age, Ethnicity, and Refractive Error

Studies show that RPE thickness can change with age and is also influenced by factors like ethnicity and vision errors. While scientists aren't completely clear on why there are differences among ethnic groups regarding RPE thickness, they suspect that skin Pigmentation could play a role.

Examining the Relationship Between RPE Thickness and Pigmentation

Research has suggested that the pigmentation of the eyes and skin can significantly affect how thick the RPE appears on OCT images. This study aimed to better understand how RPE thickness ties in with various traits linked to pigmentation. By examining both genetic factors and observable characteristics, researchers hoped to find similarities and differences between the RPE and other pigmented tissues.

The UK Biobank Study

The UK Biobank is a large health study involving over half a million participants, aiming to improve our understanding of various health issues. Participants have taken extensive surveys about their lifestyle and health, and some even had eye exams, including OCT scans. These scans provided valuable data that researchers could use to analyze RPE thickness in relation to pigmentation.

RPE Thickness and Pigmentation Scores

In order to quantify how pigmented the back part of the eye is, researchers utilized a scoring system called the retinal pigmentation score (RPS). This score mainly reflects pigment found in the choroid, which is the layer deeper than the RPE. The findings from the study revealed that RPE thickness varies greatly based on skin tone. Specifically, the results showed that individuals with darker skin had thicker RPE than those with lighter skin.

Although a weak trend showed that RPE thickness and pigmentation scores were linked, the difference was not very strong in practical terms. The researchers found no significant correlation between RPE thickness and hair or skin color.

Genetic Factors Influencing RPE Thickness

Another part of the study looked at genetic factors that could affect RPE thickness. The researchers performed genetic association studies (GWAS)-a way to identify genes linked to specific traits. They discovered several genetic variants related to pigmentation that also influence RPE thickness. One major player is the TYR gene, which is responsible for making the enzyme needed for melanin production. This gene can affect various pigmentation traits like hair color and even the risk of developing certain skin conditions.

The Surprising Lack of Correlation

While pigmentation traits showed significant connections with hair color and tanning ability, RPE thickness itself didn’t show any meaningful correlation with most of these traits. Even though RPE thickness was weakly connected to pigmentation scores, it didn't share a significant global genetic connection with many of the pigmentation traits studied. This finding points to notable differences between how pigmentation works in the RPE compared to other pigmented body tissues.

Local Genetic Relationships and RPE Thickness

Despite the overall lack of correlation, researchers noted some interesting local relationships in specific genomic regions associated with both RPE thickness and pigmentation. Genes related to pigmentation, such as TYR and OCA2, were found in these areas. However, compared to other pigmented areas of the body, these local correlations were significantly fewer. This suggests that while there may be some shared genetic factors, many differences exist between ocular and extraocular (non-eye) tissues.

Discovering Non-Pigment Related Factors

In addition to pigmentation genes, some findings pointed toward non-pigment factors that could influence RPE thickness. For instance, researchers identified genetic variants linked to age-related eye diseases. They also unveiled a connection between RPE thickness and certain lipid traits, suggesting that the balance of lipids in the body might be essential for RPE health.

Potential Causal Relationships and Future Directions

This study also indicated that specific biological markers like serum apolipoprotein B and cathepsin H could have causal effects on RPE thickness. Cathepsin H, in particular, has been implicated in several eye-related processes and may play a role in modulating RPE thickness. While this study didn’t focus directly on pigmentation in the RPE, it provided vital insights into how various factors contribute to its thickness. Future research could explore the potential roles of cathepsins in eye pigmentation further.

Conclusion

In summary, the research into RPE thickness and pigmentation provides crucial insights into the biology of the eye. It underscores how RPE thickness can be influenced by pigmentation, age, and genetic factors, while also revealing surprising differences in how pigmentation works in ocular tissues versus other body parts. Understanding these links better may contribute to future advancements in eye health and address issues related to pigmentation more effectively. And who knows-perhaps in the future, we’ll find a way to make eye doctors even more entertained than they already are. After all, making sense of the eye can be quite the sight!

Original Source

Title: Pigmentation and retinal pigment epithelium thickness: a study of the phenotypic and genotypic relationships between ocular and extraocular pigmented tissues.

Abstract: The retinal pigment epithelium (RPE) is a specialised monolayer of pigmented epithelial cells in the outer retina. The embryology and biology of pigmentation in the RPE differs from other pigmented tissues such as the hair, skin and iris. The extent to which RPE pigmentation is related to that of other tissues remains unclear, and this study aims to address this knowledge gap. Here, we utilised RPE thickness measured using optical coherence tomography (OCT) imaging as a surrogate phenotype for RPE melanin content. We used UK Biobank data to assess the phenotypic relationships between RPE thickness and fundus pigmentation (principally a measure of choroidal pigmentation), hair colour, skin colour, and ability to tan. We subsequently performed a genome-wide association study (GWAS) to identify genetic loci associated with RPE thickness. We utilised the obtained genetic data to explore the global and local genetic correlation between RPE thickness and other pigmentation-related traits. We found that RPE thickness is not phenotypically or globally genetically correlated with hair colour, skin colour or ability to tan. Whilst RPE thickness was phenotypically correlated with retinal pigmentation score, there was not significant global genetic correlation. Despite this, variants in key pigmentation loci including TYR, and OCA2-HERC2 were found to be significant in our GWAS of RPE thickness. Furthermore, we identified four genetic regions in which RPE thickness is locally genetically correlated with other pigmentation-related traits, all of which contain protein-coding genes that are central to melanogenesis and melanosome transport. In conclusion, our study supports our assertion that pigmentation plays a role in RPE thickness, and highlights both shared and divergent features of RPE and other pigmentation-related traits.

Authors: Thomas Julian, Tomas Fitzgerald, Ewan Birney, Panagiotis I. Sergouniotis

Last Update: 2024-12-07 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.12.04.626809

Source PDF: https://www.biorxiv.org/content/10.1101/2024.12.04.626809.full.pdf

Licence: https://creativecommons.org/licenses/by/4.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

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