Surreal eye with glowing retinal ganglion cells, symbolizing the connection between the immune system and neurodegeneration in glaucoma.

Decoding Glaucoma: Can We Stop the Silent Thief of Sight?

Rhea Morgan in Health & Wellness November 2025 • 4 min read.

"New research illuminates the role of the immune system in glaucoma, offering potential pathways for early detection and novel treatments to protect our vision."

Glaucoma is a neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons. This damage leads to irreversible blindness if left untreated. While high intraocular pressure (IOP) is a known risk factor, a significant percentage of glaucoma cases, known as normal-tension glaucoma (NTG), occur without elevated IOP. This makes understanding the underlying causes of glaucoma, particularly NTG, a critical area of research.

Emerging evidence suggests that the immune system plays a significant role in the development and progression of glaucoma. Studies have found elevated levels of autoantibodies against various ocular antigens in glaucoma patients, including heat shock protein 27 (HSP27) and glial cell line-derived neurotrophic factor (GDNF). These findings suggest that an autoimmune response may contribute to the damage of RGCs and the subsequent vision loss associated with glaucoma.

A recent study published in Investigative Ophthalmology & Visual Science delved deeper into this connection, investigating the effects of immunization with GDNF, both alone and in combination with HSP27, on RGC survival and retinal health in an animal model of glaucoma. The results offer valuable insights into the complex interplay between the immune system and neurodegeneration in glaucoma, paving the way for potential new therapeutic strategies.

Unveiling the Study: GDNF, HSP27, and the Autoimmune Response in Glaucoma

Surreal eye with glowing retinal ganglion cells, symbolizing the connection between the immune system and neurodegeneration in glaucoma.

The study aimed to determine whether immunization with GDNF, a neurotrophic factor, or GDNF in combination with HSP27 (GDNF+HSP) would lead to a loss of RGCs and to investigate effects on other retinal cells. Researchers immunized rats with GDNF or GDNF+HSP and then examined their retinas after four weeks to assess the impact on different cell types. They used various staining techniques and Western blot analysis to quantify RGCs, assess glial cell activation, and evaluate the health of other retinal neurons.

The researchers used male Lewis rats, randomly divided into two immunization groups (GDNF, GDNF+HSP), and a control group. They injected the rats with the respective antigens and monitored them daily for any signs of abnormalities.

RGC Count: Brn-3a and NeuN staining to quantify RGCs.
Macroglia: GFAP and vimentin staining for astrocytes and Müller cells.
Microglia Activation: Iba1 and ED1 markers to assess microglia.
Amacrine Cells: Parvalbumin and ChAT to label amacrine cells.
Photoreceptors and Bipolar Cells: Rhodopsin, opsin, PKCa, and recoverin staining.

After four weeks, the rats' eyes were examined. The retinas were stained to identify different retinal cell types and assess any changes in cell populations or protein expression levels. This detailed analysis provided a comprehensive picture of the effects of GDNF and GDNF+HSP immunization on the retina.

What This Means for Glaucoma Treatment

This research highlights the complex relationship between the immune system and glaucoma. While GDNF is typically considered a neuroprotective factor, this study suggests that, under certain conditions, it can trigger an autoimmune response that damages RGCs. The study underscores the importance of considering the immune system when developing new glaucoma treatments.

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This article is based on research published under:

DOI-LINK: 10.1167/iovs.15-18999r2, Alternate LINK

Title: Specific Inner Retinal Layer Cell Damage In An Autoimmune Glaucoma Model Is Induced By Gdnf With Or Without Hsp27

Subject: General Medicine

Journal: Investigative Opthalmology & Visual Science

Publisher: Association for Research in Vision and Ophthalmology (ARVO)

Authors: Christina Casola, Sabrina Reinehr, Sandra Kuehn, Gesa Stute, Bernhard M. Spiess, H. Burkhard Dick, Stephanie C. Joachim

Published: 2016-07-08

Everything You Need To Know

What is the primary focus of the new research on glaucoma?

The primary focus of the new research is the role of the immune system in glaucoma, exploring potential pathways for early detection and novel treatments. Specifically, it investigates the effects of immunization with GDNF, alone and in combination with HSP27, on RGC survival and retinal health. This research aims to understand the complex interplay between the immune system and neurodegeneration in glaucoma, paving the way for potential new therapeutic strategies.

How does the immune system relate to the development and progression of glaucoma?

Emerging evidence suggests a significant role of the immune system in the development and progression of glaucoma. Elevated levels of autoantibodies against ocular antigens, such as HSP27 and GDNF, have been found in glaucoma patients. The autoimmune response may contribute to the damage of RGCs, leading to vision loss. This research explores how the immune system, and specifically the use of GDNF and HSP27, may trigger or influence the progression of this condition.

What did the study investigate regarding GDNF and HSP27 in the context of glaucoma?

The study aimed to determine whether immunization with GDNF, a neurotrophic factor, or GDNF in combination with HSP27 would affect the loss of RGCs and other retinal cells. Researchers immunized rats with GDNF or GDNF+HSP and examined their retinas after four weeks using staining techniques and Western blot analysis. The researchers monitored RGC count, Macroglia, Microglia Activation, Amacrine Cells, and Photoreceptors and Bipolar Cells. This detailed analysis provided a comprehensive picture of the effects.

Why is understanding Normal-Tension Glaucoma (NTG) important in glaucoma research?

Understanding NTG is critical because a significant percentage of glaucoma cases occur without elevated IOP, a known risk factor. This makes the underlying causes of NTG a critical area of research. Current studies suggest that even if IOP is normal, other factors, like the immune response involving GDNF and HSP27, can still lead to RGC damage and vision loss. By understanding NTG, researchers can develop more effective treatments for all forms of glaucoma.

What are the implications of this research for future glaucoma treatments?

This research underscores the importance of considering the immune system when developing new glaucoma treatments. The study found that GDNF, usually considered neuroprotective, can trigger an autoimmune response that damages RGCs. This suggests that future treatments should target the immune response to protect RGCs. This research offers valuable insights and may lead to earlier detection methods, and novel therapeutic strategies by considering how HSP27 and GDNF affect RGC survival and retinal health.