RT Journal Article
SR Electronic
T1 Somatic GNAQ R183Q mutation is located within the sclera and episclera in patients with Sturge-Weber syndrome
JF British Journal of Ophthalmology
JO Br J Ophthalmol
FD BMJ Publishing Group Ltd.
SP 1006
OP 1011
DO 10.1136/bjophthalmol-2020-317287
VO 106
IS 7
A1 Yue Wu
A1 Cheng Peng
A1 Lulu Huang
A1 Li Xu
A1 Xuming Ding
A1 Yixin Liu
A1 Changjuan Zeng
A1 Hao Sun
A1 Wenyi Guo
YR 2022
UL http://bjo.bmj.com/content/106/7/1006.abstract
AB Aims To determine the correspondence between GNAQ R183Q (c.548G＞A) mutation in abnormal scleral tissue of patients with Sturge-Weber syndrome (SWS) secondary glaucoma and explore the role of GNAQ R183Q in glaucoma pathogenesis.Methods Episcleral tissues were obtained from 8 patients: SWS secondary glaucoma (n=5) and primary congenital glaucoma (PCG, n=3). Scleral tissues were obtained from 7 patients: SWS secondary glaucoma (n=2), PCG (n=1) and juvenile open-angle glaucoma (n=4). GNAQ R183Q mutation was detected in scleral tissue by droplet digital PCR. Tissue sections from SWS were examined by immunohistochemistry to determine the expression of p-ERK.Results The GNAQ R183Q mutation was present in 100% of the SWS abnormal sclera. Five cases were SWS patient-derived episcleral tissue, and the mutant allelic frequencies range from 6.9% to 12.5%. The other two were deep scleral tissues and the mutant frequencies were 1.5% and 5.3%. No mutations in GNAQ R183 codon were found in the sclera of PCG and juvenile open-angle glaucoma. Increased expression of p-ERK and p-JNK was detected in the endothelial cells of SWS abnormal scleral blood vessels.Conclusions GNAQ R183Q occurred in all abnormal scleral tissue of SWS secondary glaucoma. Increased expression of p-ERK and p-JNK in endothelial cells of blood vessels was detected in the abnormal scleral tissue. This study suggests GNAQ R183Q may regulate episcleral vessels of patients with SWS through abnormal activation of ERK and JNK, providing new genetic evidence of pathogenesis of glaucoma in SWS, and the dysplasia of scleral tissue in anterior segment may be used as an early diagnostic method or treatment targets to prevent the development and progression of glaucoma in patients with SWS.The data that support the findings of this study are available from the corresponding author on reasonable request.