Over 60 million people worldwide are diagnosed with glaucomatous optic neuropathy, which is estimated to be responsible for 8.4 million cases of irreversible blindness globally. Glaucoma is associated with characteristic damage to the optic nerve and patterns of visual field loss which principally involves the loss of retinal ganglion cells (RGCs). At present, intraocular pressure (IOP) presents the only modifiable risk factor for glaucoma, although RGC and vision loss can continue in patients despite well-controlled IOP. This, coupled with the present inability to diagnose glaucoma until relatively late in the disease process, has led to intense investigations towards the development of novel techniques for the early diagnosis of disease. This review outlines our current understanding of the potential mechanisms underlying RGC and axonal loss in glaucoma. Similarities between glaucoma and other neurodegenerative diseases of the central nervous system are drawn before an overview of recent developments in techniques for monitoring RGC health is provided, including recent progress towards the development of RGC specific contrast agents. The review concludes by discussing techniques to assess glaucomatous changes in the brain using MRI and the clinical relevance of glaucomatous-associated changes in the visual centres of the brain.

In conclusion, implantation of the iStent inject has the ability to lower the postoperative IOP significantly in POAG and PEX after a short follow-up of 6 months with a favorable risk profile. However, limitation of this surgical procedure in phakic PG may exist and need to be investigated in further studies.

Coenzyme Q10 (CoQ10) is a mitochondrial-targeted antioxidant with known neuroprotective activity. Its ocular effects when co-solubilised with α–tocopherol polyethylene glycol succinate (TPGS) were evaluated. In vitro studies confirmed that CoQ10 was significantly protective in different retinal ganglion cell (RGC) models. In vivo studies in Adult Dark Agouti (DA) rats with unilateral surgically-induced ocular hypertension (OHT) treated with either CoQ10/TPGS micelles or TPGS vehicle twice daily for three weeks were performed, following which retinal cell health was assessed in vivo using DARC (Detection of Apoptotic Retinal Cells) and post-mortem with Brn3a histological assessment on whole retinal mounts. CoQ10/TPGS showed a significant neuroprotective effect compared to control with DARC (p < 0.05) and Brn3 (p < 0.01). Topical CoQ10 appears an effective therapy preventing RGC apoptosis and loss in glaucoma-related models.

Parkinson’s Disease (PD) is the second most common neurodegenerative disease worldwide, affecting 1 % of the population over 65 years of age. Dopaminergic cell death in the substantia nigra and accumulation of Lewy bodies are the defining neuropathological hallmarks of the disease. Neuronal death and dysfunction have been reported in other central nervous system regions, including the retina. Symptoms of PD typically manifest only when more than 70 % of dopaminergic cells are lost, and the definitive diagnosis of PD can only be made histologically at post-mortem, with few biomarkers available.In this study, a rotenone-induced rodent model of PD was employed to investigate retinal manifestations in PD and their usefulness in assessing the efficacy of a novel therapeutic intervention with a liposomal formulation of the PPAR-γ (Peroxisome proliferator-activated receptor gamma) agonist rosiglitazone.Retinal assessment was performed using longitudinal in vivo imaging with DARC (detection of apoptosing retinal cells) and OCT (optical coherence tomography) technologies and revealed increased RGCs (Retinal Ganglion Cells) apoptosis and a transient swelling of the retinal layers at day 20 of the rotenone insult. Follow-up of this model demonstrated characteristic histological neurodegenerative changes in the substantia nigra and striatum by day 60, suggesting that retinal changes precede the “traditional” pathological manifestations of PD. The therapeutic effect of systemic administration of different formulations of rosiglitazone was then evaluated, both in the retina and the brain. Of all treatment regimen tested, sustained release administration of liposome-encapsulated rosiglitazone proved to be the most potent therapeutic strategy, as evidenced by its significant neuroprotective effect on retinal neurons at day 20, and on nigrostriatal neurons at day 60, provided convincing evidence for its potential as a treatment for PD.Our results demonstrate significant retinal changes occurring in this model of PD. We show that rosiglitazone can efficiently protect retinal neurons from the rotenone insult, and that systemic administration of liposome-encapsulated rosiglitazone has an enhanced neuroprotective effect on the retina and CNS (Central Nervous System). To our knowledge, this is the first in vivo evidence of RGCs loss and early retinal thickness alterations in a PD model. Together, these findings suggest that retinal changes may be a good surrogate biomarker for PD, which may be used to assess new treatments both experimentally and clinically.

Curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5dione) is a polyphenol extracted from turmeric that has long been advocated for the treatment of a variety of conditions including neurodegenerative and inflammatory disorders. Despite this promise, the clinical use of curcumin has been limited by the poor solubility and low bioavailability of this molecule. In this article, we describe a novel nanocarrier formulation comprising Pluronic-F127 stabilised D-α-Tocopherol polyethene glycol 1000 succinate nanoparticles, which were used to successfully solubilize high concentrations (4.3 mg/mL) of curcumin. Characterisation with x-ray diffraction and in vitro release assays localise curcumin to the nanocarrier interior, with each particle measuring <20 nm diameter. Curcumin-loaded nanocarriers (CN) were found to significantly protect against cobalt chloride induced hypoxia and glutamate induced toxicity in vitro, with CN treatment significantly increasing R28 cell viability. Using established glaucoma-related in vivo models of ocular hypertension (OHT) and partial optic nerve transection (pONT), topical application of CN twice-daily for three weeks significantly reduced retinal ganglion cell loss compared to controls. Collectively, these results suggest that our novel topical CN formulation has potential as an effective neuroprotective therapy in glaucoma and other eye diseases with neuronal pathology.

Ab interno trabeculectomy and iStent® inject were both effective in lowering IOP with a favourable and comparable safety profile in an intraindividual comparative study over a 12-months follow-up in OAG. However, longer follow-up of these patients will be necessary to determine long-term outcomes and to evaluate significant differences.

Glaucoma is the second leading cause of blindness worldwide and is most notably characterized by progressive optic nerve atrophy and advancing loss of retinal ganglion cells (RGCs). The main concomitant factor is the elevated intraocular pressure (IOP). Existing treatments are focused generally on lowering IOP. However, both RGC loss and optic nerve atrophy can independently occur with IOP at normal levels. In recent years, there has been substantial progress in the development of neuroprotective therapies for glaucoma in order to restore vital visual function. The present review intends to offer a brief insight into conventional glaucoma treatments and discuss exciting current developments of mostly preclinical data in novel neuroprotective strategies for glaucoma that include recent advances in noninvasive diagnostics going beyond IOP maintenance for an enhanced global view. Such strategies now target RGC loss and optic nerve damage, opening a critical therapeutic window for preventative monitoring and treatment.

In celiac disease, the gut-associated immune system is activated in response to the ingestion of gluten, causing an atrophy of the small intestinal mucosa. Although this condition is, in most cases, responsive to a gluten-free diet, celiac disease refractory to treatment occurs in a small percentage of celiacs. An epithelial barrier defect is known to be an integral part of celiac pathophysiology. However, the mucosa in refractory celiac disease underlies a constant inflammatory process. The epithelial barrier has not been addressed in this condition so far. Herein, the tight junction-associated barrier in refractory celiac disease is investigated functionally and structurally. Although normally expressed in celiac disease, claudin-4 is shown to be downregulated in refractory cases, presumably by two mechanisms, reduced protein expression and increased claudin endocytosis. Furthermore, the tightening claudin-5 is downregulated and the pore-forming claudin-2 is upregulated.