Angiogenesis, disruption of the retinal barrier, leukocyte‐adhesion and oedema are cardinal signs of proliferative retinopathies that are associated with vision loss. Therefore, identifying factors that regulate these vascular dysfunctions is critical to target pathological angiogenesis. Given the conflicting role of bioactive lipids reported in the current literature, the goal of this review is to provide the reader a clear road map of what has been accomplished so far in the field with specific focus on the role of polyunsaturated fatty acids (PUFAs)‐derived metabolites in proliferative retinopathies. This necessarily entails a description of the different retina cells, blood retina barriers and the role of (PUFAs)‐derived metabolites in diabetic retinopathy, retinopathy of prematurity and age‐related macular degeneration as the most common types of proliferative retinopathies.

PurposeTraumatic optic neuropathy (TON) is the most feared visual consequence of head and ocular trauma in both military and civilian communities, for which standard treatment does not exist. Animal models are critical for the development of novel TON therapies as well as the understanding of TON pathophysiology. However, the models currently used for TON have some limitations regarding consistency and mirroring the exact pathological progression of TON in closed ocular trauma. In this study, we modified the model of controlled cortical impact and adapted it for studying TON.MethodsWe defined new standardized procedures to induce TON in mice, wherein the optic nerve is reproducibly exposed to a graded controlled impact of known velocity to produce a graded deficit in retinal ganglion cell (RGC) electrophysiological functions.ResultsThe key results of validating this newly modified model, “controlled orbital impact (COI),” included (1) the injury parameters (velocity as well as contusion depth and time), which were quantifiable and manageable to generate a wide range of TON severities; (2) a reproducible endpoint of diminished positive scotopic threshold response (pSTR) has been achieved without the interference of surgical variability and destruction of surrounding tissues; (3) the contralateral eyes showed no significant difference to the eyes of naïve mice, allowing them to be used as an internal control to minimize interindividual variability among mice; and (4) the occurrence of injury-associated mortality and/or ocular comorbidity was rare.ConclusionsTaken together, this model overcomes some limitations of prior TON mouse models and provides an innovative platform to identify therapeutic targets for neuroprotection and/or neurorestoration following traumatic ocular injury.

Purpose: Diabetic retinopathy (DR) is a neurovascular complication of diabetes with critical limitations in current treatment due to a lack of neuroprotection. These limitations mandate the necessity for new therapy that considers the neuronal component of DR. The goal of this study is to explore the role of 12/15-lipoxygenase (LO) in diabetes-induced retinal neuronal dysfunction. Methods: 12/15-LO deficient (12/15-LO−/−) mice were crossbred with Ins2Akita/+ Akita) mice, a classical model of DR, to generate a new mouse model with a double knockout (12/15-LO−/−/Akita). The generated mice were subjected to comprehensive electroretinogram (ERG) analyses after 6 months of diabetes. Results: Profound effects of knocking 12/15-LO out on diabetes-induced reduction in visual system’s functionality were observed. First, Scotopic Threshold Response (pSTR) peak heights, which measure the functionality of ganglion cells (GCs), are consistently lower in Akita than in wild type (WT) mice. Knocking 12/15-LO out significantly improved the overall pSTR and significantly restored the loss of the GC marker (Brn3) as compared with Akita mice. Second, diabetes reduced the functionality of cone-bipolar cells by 32%, as assessed by photopic B-Wave (pBW) amplitudes, however, this reduction was significantly improved in 12/15-LO−/−/Akita mice compared with Akita mice (p<0.05, n=9). Lastly, diabetes caused a significant reduction (22%) in cone photoreceptor functionality as indicated by a lower response to natural noise stimuli (NNS) in Akita compared to WT mice (p<0.05, n=8) and this reduction was completely recovered in 12/15-LO−/−/Akita mice (p<0.05, n=9). Conclusion: To our knowledge, this is the first report that elimination of 12/15-LO protects against diabetes-induced visual system dysfunction. The findings may lead to new therapeutic approaches in prevention and treatment of DR. Disclosure M. Wan: None. A. Ibrahim: None. M. El-Shafey: None. K. Elmasry: None. S. Abdulmoneim: None. A. Saul: None. M. Al-Shabrawey: None.