Developmental basis of nanophthalmos: MFRP is required for both prenatal ocular growth and postnatal emmetropization

Olof H. Sundin, Sharola Dharmaraj, Imran A. Bhutto, Takuya Hasegawa, D. Scott McLeod, Carol A. Merges, Eduardo D. Silval, Irene H. Maumenee, Gerard Anthony Lutty

Research output: Contribution to journalArticle

Abstract

Background: Nanophthalmos is a genetic disorder characterized by very small, hyperopic eyes that are without gross structural defects. Recessive nanophthalmos is caused by severe mutations in the MFRP gene, which encodes a Frizzled-related transmembrane protein that is selectively expressed in the retinal pigment epithelium (RPE) and ciliary body. Results: For two MFRP -/- adults, we have obtained records of refraction that begin in early childhood. At the age of 6 months, one patient's eyes already had a refractive error of +12.25 D, and over the next 20 years this slowly increased to +17.50 D. Adults homozygous for null mutations in MFRP have eyes with axial lengths shorter than those of normal newborns. Furthermore, the unusually high curvature of their corneas is consistent with eyes that had been smaller than normal during late fetal development. MFRP protein was first detected at 14 weeks of gestation, when it was restricted to the posterior pole RPE. By 20 weeks gestation, MFRP expression had spread laterally, and was found throughout the RPE. MFRP protein was detected in both posterior and lateral RPE of the adult eye. Conclusions: Embryonic function of the MFRP gene appears necessary for the eye to reach its full size at birth. Its onset of expression in the RPE during mid-gestation suggests that MFRP does not participate in early formation of the optic cup, and is consistent with a role in later growth and development of the eye. Patients without MFRP gene function exhibit no correction of refractive error during childhood, which suggests that this gene is essential for emmetropization, a complex process by which vision regulates axial growth of the eye.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalOphthalmic Genetics
Volume29
Issue number1
DOIs
StatePublished - Mar 2008

Fingerprint

Retinal Pigment Epithelium
Growth
Refractive Errors
Pregnancy
Pigment Epithelium of Eye
Eye Axial Length
Genes
Ciliary Body
Mutation
Inborn Genetic Diseases
Essential Genes
Fetal Development
Growth and Development
Cornea
Proteins
Parturition
Newborn Infant

Keywords

  • Development
  • Hyperopia
  • Microphthalmia
  • Nanophthalmos

ASJC Scopus subject areas

  • Ophthalmology
  • Pediatrics, Perinatology, and Child Health
  • Genetics(clinical)

Cite this

Developmental basis of nanophthalmos : MFRP is required for both prenatal ocular growth and postnatal emmetropization. / Sundin, Olof H.; Dharmaraj, Sharola; Bhutto, Imran A.; Hasegawa, Takuya; McLeod, D. Scott; Merges, Carol A.; Silval, Eduardo D.; Maumenee, Irene H.; Lutty, Gerard Anthony.

In: Ophthalmic Genetics, Vol. 29, No. 1, 03.2008, p. 1-9.

Research output: Contribution to journalArticle

Sundin, Olof H. ; Dharmaraj, Sharola ; Bhutto, Imran A. ; Hasegawa, Takuya ; McLeod, D. Scott ; Merges, Carol A. ; Silval, Eduardo D. ; Maumenee, Irene H. ; Lutty, Gerard Anthony. / Developmental basis of nanophthalmos : MFRP is required for both prenatal ocular growth and postnatal emmetropization. In: Ophthalmic Genetics. 2008 ; Vol. 29, No. 1. pp. 1-9.
@article{33b62e0007f24d77abf853e9f2538efb,
title = "Developmental basis of nanophthalmos: MFRP is required for both prenatal ocular growth and postnatal emmetropization",
abstract = "Background: Nanophthalmos is a genetic disorder characterized by very small, hyperopic eyes that are without gross structural defects. Recessive nanophthalmos is caused by severe mutations in the MFRP gene, which encodes a Frizzled-related transmembrane protein that is selectively expressed in the retinal pigment epithelium (RPE) and ciliary body. Results: For two MFRP -/- adults, we have obtained records of refraction that begin in early childhood. At the age of 6 months, one patient's eyes already had a refractive error of +12.25 D, and over the next 20 years this slowly increased to +17.50 D. Adults homozygous for null mutations in MFRP have eyes with axial lengths shorter than those of normal newborns. Furthermore, the unusually high curvature of their corneas is consistent with eyes that had been smaller than normal during late fetal development. MFRP protein was first detected at 14 weeks of gestation, when it was restricted to the posterior pole RPE. By 20 weeks gestation, MFRP expression had spread laterally, and was found throughout the RPE. MFRP protein was detected in both posterior and lateral RPE of the adult eye. Conclusions: Embryonic function of the MFRP gene appears necessary for the eye to reach its full size at birth. Its onset of expression in the RPE during mid-gestation suggests that MFRP does not participate in early formation of the optic cup, and is consistent with a role in later growth and development of the eye. Patients without MFRP gene function exhibit no correction of refractive error during childhood, which suggests that this gene is essential for emmetropization, a complex process by which vision regulates axial growth of the eye.",
keywords = "Development, Hyperopia, Microphthalmia, Nanophthalmos",
author = "Sundin, {Olof H.} and Sharola Dharmaraj and Bhutto, {Imran A.} and Takuya Hasegawa and McLeod, {D. Scott} and Merges, {Carol A.} and Silval, {Eduardo D.} and Maumenee, {Irene H.} and Lutty, {Gerard Anthony}",
year = "2008",
month = "3",
doi = "10.1080/13816810701651241",
language = "English (US)",
volume = "29",
pages = "1--9",
journal = "Ophthalmic Genetics",
issn = "1381-6810",
publisher = "Aeolus Press",
number = "1",

}

TY - JOUR

T1 - Developmental basis of nanophthalmos

T2 - MFRP is required for both prenatal ocular growth and postnatal emmetropization

AU - Sundin, Olof H.

AU - Dharmaraj, Sharola

AU - Bhutto, Imran A.

AU - Hasegawa, Takuya

AU - McLeod, D. Scott

AU - Merges, Carol A.

AU - Silval, Eduardo D.

AU - Maumenee, Irene H.

AU - Lutty, Gerard Anthony

PY - 2008/3

Y1 - 2008/3

N2 - Background: Nanophthalmos is a genetic disorder characterized by very small, hyperopic eyes that are without gross structural defects. Recessive nanophthalmos is caused by severe mutations in the MFRP gene, which encodes a Frizzled-related transmembrane protein that is selectively expressed in the retinal pigment epithelium (RPE) and ciliary body. Results: For two MFRP -/- adults, we have obtained records of refraction that begin in early childhood. At the age of 6 months, one patient's eyes already had a refractive error of +12.25 D, and over the next 20 years this slowly increased to +17.50 D. Adults homozygous for null mutations in MFRP have eyes with axial lengths shorter than those of normal newborns. Furthermore, the unusually high curvature of their corneas is consistent with eyes that had been smaller than normal during late fetal development. MFRP protein was first detected at 14 weeks of gestation, when it was restricted to the posterior pole RPE. By 20 weeks gestation, MFRP expression had spread laterally, and was found throughout the RPE. MFRP protein was detected in both posterior and lateral RPE of the adult eye. Conclusions: Embryonic function of the MFRP gene appears necessary for the eye to reach its full size at birth. Its onset of expression in the RPE during mid-gestation suggests that MFRP does not participate in early formation of the optic cup, and is consistent with a role in later growth and development of the eye. Patients without MFRP gene function exhibit no correction of refractive error during childhood, which suggests that this gene is essential for emmetropization, a complex process by which vision regulates axial growth of the eye.

AB - Background: Nanophthalmos is a genetic disorder characterized by very small, hyperopic eyes that are without gross structural defects. Recessive nanophthalmos is caused by severe mutations in the MFRP gene, which encodes a Frizzled-related transmembrane protein that is selectively expressed in the retinal pigment epithelium (RPE) and ciliary body. Results: For two MFRP -/- adults, we have obtained records of refraction that begin in early childhood. At the age of 6 months, one patient's eyes already had a refractive error of +12.25 D, and over the next 20 years this slowly increased to +17.50 D. Adults homozygous for null mutations in MFRP have eyes with axial lengths shorter than those of normal newborns. Furthermore, the unusually high curvature of their corneas is consistent with eyes that had been smaller than normal during late fetal development. MFRP protein was first detected at 14 weeks of gestation, when it was restricted to the posterior pole RPE. By 20 weeks gestation, MFRP expression had spread laterally, and was found throughout the RPE. MFRP protein was detected in both posterior and lateral RPE of the adult eye. Conclusions: Embryonic function of the MFRP gene appears necessary for the eye to reach its full size at birth. Its onset of expression in the RPE during mid-gestation suggests that MFRP does not participate in early formation of the optic cup, and is consistent with a role in later growth and development of the eye. Patients without MFRP gene function exhibit no correction of refractive error during childhood, which suggests that this gene is essential for emmetropization, a complex process by which vision regulates axial growth of the eye.

KW - Development

KW - Hyperopia

KW - Microphthalmia

KW - Nanophthalmos

UR - http://www.scopus.com/inward/record.url?scp=41149103946&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41149103946&partnerID=8YFLogxK

U2 - 10.1080/13816810701651241

DO - 10.1080/13816810701651241

M3 - Article

C2 - 18363166

AN - SCOPUS:41149103946

VL - 29

SP - 1

EP - 9

JO - Ophthalmic Genetics

JF - Ophthalmic Genetics

SN - 1381-6810

IS - 1

ER -