Gap junctions (GJs) are not static bridges; instead, GJs as well as the molecular building block connexin (Cx) proteins undergo major expression changes in the degenerating retinal tissue. Various progressive diseases, including retinitis pigmentosa, glaucoma, age-related retinal degeneration, etc., affect neurons of the retina and thus their neuronal connections endure irreversible changes as well. Although Cx expression changes might be the hallmarks of tissue deterioration, GJs are not static bridges and as such they undergo adaptive changes even in healthy tissue to respond to the ever-changing environment. It is, therefore, imperative to determine these latter adaptive changes in GJ functionality as well as in their morphology and Cx makeup to identify and distinguish them from alterations following tissue deterioration. In this review, we summarize GJ alterations that take place in healthy retinal tissue and occur on three different time scales: throughout the entire lifespan, during daily changes and as a result of quick changes of light adaptation.

Traumatic brain injury (TBI) induces complex molecular and cellular responses, often leading to vision deterioration and potential mortality. Current objective diagnostic methods are limited, necessitating the development of novel tools to assess disease severity. This review focuses on the retina, a readily approachable part of the central nervous system (CNS), as a potential indicator of TBI. We conduct a targeted database search and employ a blinded scoring system, incorporating both human and artificial intelligence (AI) assessments, to identify relevant articles. We then perform a detailed analysis to elucidate the molecular pathways and cellular changes in the retina following TBI. Recent findings highlight the involvement of key molecular markers, such as ionized calcium-binding adapter molecule 1 (IBA1), phosphorylated tau, glial fibrillary acidic protein (GFAP), and various cytokines (IL-1β, IL-6, and TNF). Additionally, the roles of oxidative stress, reactive oxygen species (ROS), and blood–retina barrier (BRB) disruption are explored. Based on these findings, we hypothesize that alterations in these molecular pathways and cellular components, particularly microglia, can serve as direct indicators of brain health and TBI severity. Recent technological advancements in retinal imaging now allow for a direct assessment of retinal cells, including microglia, and related inflammatory processes, facilitating the translation of these molecular findings into clinical practice. This review underscores the retina’s potential as a non-invasive window into the molecular pathophysiology of TBI.

Traumatic brain injury (TBI) represents a significant medical concern typically resulting from severe or repetitive mild head impacts. It often results in vision deterioration and can cause sudden death after hospitalization as a result of pathologies. The objective identification options are limited or too invasive to be routinely applied; therefore, we need new tools to identify the severity of the disease. The retina is the only part of the central nervous system that is directly approachable by light and easy to access. In this review, we used an aimed database search, together with a blinded human and artificial intelligence (AI) based scoring system to narrow down the number of articles, based on relevance to the topic. The selected articles went through thorough processing to identify the relevant links in them. Based on this, we hypothesize that the retina can be used as a direct indicator of brain health, including the use of microglia to indicate traumatic brain injury. As an outcome, we concluded that recent developments in technology now allow the imaging of the retinal surface and cells directly to allow retinal cellular and inflammatory assessment and translation of the findings into medical practice.

Traumatic brain injury (TBI) induces rapid neuroinflammatory responses not only in the brain but also in anatomically and immunologically connected central nervous system (CNS) compartments, including the retina. In our study, we investigated retinal microglial activation, retinal ganglion cell (RGC) calcium dynamics, and caspase-3 activation in adult mice subjected to severe traumatic brain injury using the Marmarou impact-acceleration model at 24 and 48 h post-injury. Carrying out Ca²⁺-imaging, immunohistochemistry, and ex vivo time-lapse microscopy, we found robust microglial activation in both the superficial and deep retinal layers following TBI, accompanied by increased microglial motility. RGCs exhibited a transient surge in degeneration-induced spontaneous activity at 24 h, followed by a marked reduction below control levels at 48 h, consistent with early degenerative changes. Activated caspase-3 levels were significantly elevated in both microglia and other retinal cell types at both time points, indicating ongoing apoptotic effects. Together, these findings demonstrate that TBI rapidly triggers inflammatory and apoptotic mechanisms in the retina, which are detectable within the first 48 hours. Our results highlight the retina as a sensitive indicator of early CNS pathology after traumatic injury and underscore the potential of retinal analysis for monitoring TBI-induced neurodegeneration for future clinical implementation. Graphical