Human Molecular Genetics, 2017, Vol. 26, No.
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Editorial
The molecular genetics of eye diseases
This review issue of Human Molecular Genetics focuses on the
eye. Perhaps the study of no other organ system has benefited
more from the combination of the results of the Human
Genome Project and recent progress in molecular biology.
Conversely, the study of the eye has provided great insight into
disease pathophysiology and the understanding of genomics.
These statements are not surprising when one considers the
following facts: (i) the eye is composed of many cell types, and
approximately 90% of the genes in the human genome are ex-
pressed in one or more of the many tissues composing the eye
during development and/or in maturity; and (ii) approximately
one-third of the clinical disorders catalogued in Online
Mendelian Inheritance in Man (OMIM) list a feature involving
the eye (1). Progress has been made in understanding inherited
eye diseases displaying nearly every type of inheritance pattern
including X-linked, autosomal dominant and recessive, mito-
chondrial, digenic and complex. In fact, several eye diseases dis-
play all of these inheritance patterns.
Advantages in studying eye pathophysiology and function
include the facts that eye disease can result in a noticeable defi-
cit observable by the patient or the patient’s parents even at a
young age; and ophthalmologists can readily and non-
invasively evaluate eye anatomy and key structures with oph-
thalmoscopy, electrophysiology, and more recently, with optical
coherence tomography (OCT). Application of state-of-the-art
molecular genetics and molecular biology to inherited eye disor-
ders including positional cloning methods, genome-wide asso-
ciation studies, and whole exome sequencing has led to the
discovery of hundreds of genes and thousands of mutations in
hundreds of diseases. A review of the topic in Human Molecular
Genetics is long overdue.
Reviewed in the various articles in this issue of HMG are topics
impacting many aspects of this complex organ including photore-
ceptors and the photoreceptor outer segment; retinopathies;
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doi: 10.1093/hmg/ddx222
Editorial
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macular degeneration; corneal diseases; congenital, developmen-
tal and primary open angle glaucomas; the complement system
in eye disease; mitochondrial dysfunction; ocular congenital dys-
innervation disorders; genetic modifiers of eye phenotypes, and
others. Important points to observe as one reads the articles are
the large variety of disorders impacting the eye, the diversity of
phenotypes and ages of onset observable even with mutations in
the same gene, and in other instances, the diversity of genes re-
sulting in the same or very similar clinical presentations. Also ap-
parent in the molecular genetics of inherited eye diseases, as in
most fields of medicine and science, is the fact that many chal-
lenges remain in developing treatments for eye diseases, perhaps
none greater than the development of cost effective molecular
therapies (2) for these disorders that impact the quality of life for
many patients. Hope lies in the fact that many features of the eye
make it an outstanding target for molecular and cell therapies
and that novel approaches have been and are being developed.
Jonathan L. Haines1,* and Val C. Sheffield2,*
1
Department of Population & Quantitative Health Sciences, Case
Western Reserve University Cleveland, OH, USA and 2Departments of
Pediatrics and Ophthalmology & Visual Sciences, University of Iowa
Carver College of Medicine, Iowa City, IA, USA
*Correspondence to be addressed: Tel: 216-368-2478; Email:
jlh213@case.edu (J.H.); val-sheffield@uiowa.edu (V.S.)
References
1. Sheffield, V.C. and Sone, E.M. (2011) Genomics and the eye. N.
Engl. J. Med., 364, 1932–1942.
2. Orkin, S.H. and Reily, P. (2016) Paying for the future success in
gene therapy. Science, 352, 1059–1061.
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