Background: Retinal ganglion cell (RGC) degeneration is a major feature of glaucoma
pathology. Neuroprotective approaches that delay or halt the progression of RGC loss are needed to
prevent vision loss which can occur even after conventional medical or surgical treatments to lower
Objective: The aim of this review was to examine the progress in genetics and cellular mechanisms
associated with endoplasmic reticulum (ER) stress, RGC dysfunction and cell death pathways in
Materials and Methods: Here, we review the involvement of neurotrophins like brain derived neurotrophic
factor (BDNF) and its high affinity receptor tropomyosin receptor kinase (TrkB) in glaucoma.
The role of ER stress markers in human and animal retinas in health and disease conditions is
also discussed. Further, we analysed the literature highlighting genetic linkage in the context of
primary open angle glaucoma and suggested mechanistic insights into potential therapeutic options
relevant to glaucoma management.
Results: The literature review of the neurobiology underlying neurotrophin pathways, ER stress and
gene associations provide critical insights into association of RGCs death in glaucoma. Alteration in
signalling pathway is associated with increased risk of misfolded protein aggregation in ER promoting
RGC apoptosis. Several genes that are linked with neurotrophin signalling pathways have been
reported to be associated with glaucoma pathology.
Conclusion: Understanding genetic heterogeneity and involvement of neurotrophin biology in
glaucoma could help to understand the complex pathophysiology of glaucoma. Identification of
novel molecular targets will be critical for drug development and provide neuroprotection to the
RGCs and optic nerve.