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Limbal Approach-Subretinal Injection of Viral Vectors for Gene Therapy in Mice Retinal Pigment Epithelium
Published on: August 7, 2015
LAG3 Gene Therapy Attenuates Autoimmune Uveitis by Regulating the PI3K/Akt Signaling Pathway
Liu Zheng1, Jiaojiao Jiang1, Qiujin Zhang2
1Department of Ophthalmology, The First Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China.
Investigative Ophthalmology & Visual Science
|July 22, 2026
Summary
Lymphocyte-activation gene 3 (LAG3) is downregulated in autoimmune uveitis. Gene therapy with AAV2-LAG3 reduced disease severity by modulating the PI3K/Akt pathway and restoring immune balance.
Area of Science:
- Immunology
- Ophthalmology
- Molecular Biology
Background:
- Lymphocyte-activation gene 3 (LAG3) is an immune checkpoint molecule.
- Its role in autoimmune uveitis is not well understood.
- Understanding LAG3 in autoimmune uveitis is crucial for developing new therapies.
Purpose of the Study:
- To investigate the expression dynamics of LAG3 in experimental autoimmune uveitis (EAU).
- To evaluate the therapeutic potential of AAV2-LAG3 in EAU.
- To elucidate the molecular mechanisms underlying LAG3's function in EAU.
Main Methods:
- Established EAU model in C57BL/6J mice.
- Administered AAV2-LAG3 via intravitreal injection.
- Assessed disease severity, blood-retinal barrier (BRB) integrity, and molecular pathways (RNA-seq, Western blot, qPCR).
Main Results:
- Retinal LAG3 expression decreased during peak EAU inflammation.
- AAV2-LAG3 treatment significantly reduced EAU severity and preserved BRB integrity.
- LAG3's protective effects were linked to PI3K/Akt pathway modulation and Th17/Treg cell balance restoration.
Conclusions:
- LAG3 expression is downregulated in EAU.
- AAV2-LAG3 therapy shows promise for treating autoimmune uveitis.
- LAG3 attenuates EAU by regulating PI3K/Akt signaling and immune homeostasis.
