TY - JOUR
T1 - Genetic predisposition to ocular surface disorders and opportunities for gene-based therapies
AU - Roshandel, Danial
AU - Semnani, Farbod
AU - Damavandi, Amirmasoud Rayati
AU - Masoudi, Ali
AU - Baradaran-Rafii, Alireza
AU - Watson, Stephanie L.
AU - Morgan, William H.
AU - McLenachan, Samuel
PY - 2023/7
Y1 - 2023/7
N2 - The ocular surface, comprised of the corneal and conjunctival epithelium, innervation system, immune components, and tear-film apparatus, plays a key role in ocular integrity as well as comfort and vision. Gene defects may result in congenital ocular or systemic disorders with prominent ocular surface involvement. Examples include epithelial corneal dystrophies, aniridia, ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome, xeroderma pigmentosum (XP), and hereditary sensory and autonomic neuropathy. In addition, genetic factors may interact with environmental risk factors in the development of several multifactorial ocular surface disorders (OSDs) such as autoimmune disorders, allergies, neoplasms, and dry eye disease. Advanced gene-based technologies have already been introduced in disease modelling and proof-of-concept gene therapies for monogenic OSDs. For instance, patient-derived induced pluripotent stem cells have been used for modelling aniridia-associated keratopathy (AAK), XP, and EEC syndrome. Moreover, CRISPR/Cas9 genome editing has been used for disease modelling and/or gene therapy for AAK and Meesmann's epithelial corneal dystrophy. A better understanding of the role of genetic factors in OSDs may be helpful in designing personalized disease models and treatment approaches. Gene-based approaches in monogenic OSDs and genetic predisposition to multifactorial OSDs such as immune-mediated disorders and neoplasms with known or possible genetic risk factors has been seldom reviewed. In this narrative review, we discuss the role of genetic factors in monogenic and multifactorial OSDs and potential opportunities for gene therapy.
AB - The ocular surface, comprised of the corneal and conjunctival epithelium, innervation system, immune components, and tear-film apparatus, plays a key role in ocular integrity as well as comfort and vision. Gene defects may result in congenital ocular or systemic disorders with prominent ocular surface involvement. Examples include epithelial corneal dystrophies, aniridia, ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome, xeroderma pigmentosum (XP), and hereditary sensory and autonomic neuropathy. In addition, genetic factors may interact with environmental risk factors in the development of several multifactorial ocular surface disorders (OSDs) such as autoimmune disorders, allergies, neoplasms, and dry eye disease. Advanced gene-based technologies have already been introduced in disease modelling and proof-of-concept gene therapies for monogenic OSDs. For instance, patient-derived induced pluripotent stem cells have been used for modelling aniridia-associated keratopathy (AAK), XP, and EEC syndrome. Moreover, CRISPR/Cas9 genome editing has been used for disease modelling and/or gene therapy for AAK and Meesmann's epithelial corneal dystrophy. A better understanding of the role of genetic factors in OSDs may be helpful in designing personalized disease models and treatment approaches. Gene-based approaches in monogenic OSDs and genetic predisposition to multifactorial OSDs such as immune-mediated disorders and neoplasms with known or possible genetic risk factors has been seldom reviewed. In this narrative review, we discuss the role of genetic factors in monogenic and multifactorial OSDs and potential opportunities for gene therapy.
KW - Gene therapy
KW - Genetic predisposition
KW - Ocular surface disorder
UR - http://www.scopus.com/inward/record.url?scp=85160046532&partnerID=8YFLogxK
U2 - 10.1016/j.jtos.2023.05.003
DO - 10.1016/j.jtos.2023.05.003
M3 - Review article
C2 - 37192706
SN - 1542-0124
VL - 29
SP - 150
EP - 165
JO - The Ocular Surface
JF - The Ocular Surface
ER -