IDENTIFYING GLAUCOMA

Immunoproteomics may soon provide an easy, non-invasive and objective means of diagnosing glaucomatous disease and may also point to new approaches to therapy, Franz Grus MD, PhD, Medical University Mainz, Mainz, Germany told the 11th Congress of the European Glaucoma Society in Nice.

He noted that, in several clinical studies so far involving populations from Germany, the US or Australia, he and his associates were able to detect glaucoma with a sensitivity and specificity of more than 90 per cent based solely on their autoantibody profiles. “Our findings from these antibody tests could also open up the way to the development of innovative personalised immunomodulatory treatment options.”

Proteomes and glaucoma

Dr Grus noted that “proteomics” corresponds to proteins as “genomics” corresponds to genes. A good illustration of the importance of proteomics is the transformation of caterpillar to a butterfly. Although the genome remains the same, the proteome is vastly altered from one stage to the other.

Many proteomic biomarkers have been identified for glaucoma, like for example the presence of transthyretin in the aqueous humour and sphingomyelin in the optic nerve. However, there are as yet no non-invasive means of testing for these biomarkers, Dr Grus said.

“The disadvantage of most of these proteomic markers is that they are not easily accessible because they are coming from aqueous humour and optic nerve and the retina. Therefore we asked ourselves if immunoproteomics from easily accessible body fluids, like tears or blood, could be a way to look at it because antibodies are stable and very easy to measure,” he said.

Dr Grus said that studies comparing the immunoreactivity of serum from glaucoma patients and control patients show that there are consistent changes in the autoantibody profile in patients with glaucoma. He noted that glaucoma patients and controls have very complex immunoreactivity patterns and a very high number of antibodies that react with antigens from the optic nerve and retina. The increase (up regulation) and decrease (down regulation) in the production of these autoantibodies in patients with glaucoma may have both a cause and an effect relationship with the disease, he said.

Animal studies on Lewis rats proved the neurodegenerative properties of an induced autoimmunity conducted through systemic immunisation of previously identified antigens and resulted in retinal ganglion cell loss. Using this Experimental Autoimmune Glaucoma (EAG) animal model Dr Grus was able to demonstrate that also a complex alteration in the autoantibody patterns was provoked in these animals and the animals developed a glaucomatous autoantibody profile.

Recent new immunohistological findings in patients with glaucoma include antibody deposits in their retinal ganglion cell layer, microglial activation and probably activation of B lymphocytes.

Franz Grus: grus@eye-research.org