Recognising and managing retinal detachments.

Retinal detachments are a potentially sight-threatening ophthalmic emergency that may result in significant, irreversible vision loss. The risk of developing retinal detachment increases with advancing age, myopia and trauma. Pre-existing retinal degenerations can precipitate a pre-detachment symptomatic period of photopsia or floaters, allowing clinicians to intervene early and prevent detachments. Novel imaging techniques, such as spectral-domain optical coherence tomography, and well-established topographic modalities, such as B scan, can help to elucidate the type of detachment and any underlying causes, and help with surgical management. The overarching goal of treatment is to identify and seal all retinal holes, relieve vitreoretinal traction and prevent further recurrence. Prompt prophylactic retinopexy of retinal holes and tears is crucial in preventing retinal detachment, the main treatments of which are pars plana vitrectomy, tamponading agents and silicone scleral buckle.

A routinely used protein staining dye acts as an inhibitor of wild type and mutant alpha-synuclein aggregation and modulator of neurotoxicity.

Inhibition of amyloid formation along with modulation of toxicity employing small molecules is emerging as a potential therapeutic approach for protein misfolding disorders which includes Parkinson's disease, Alzheimer's disease and Multiple System Atrophy etc. Countless current interventional strategies for treating α-synucleinopathies consider using peptidic and non-peptidic inhibitors for arresting fibrillisation, disrupting existing fibrils and reducing associated toxicity. One group of molecules less exploited in this regard are triphenylmethane dyes. Herein we tested the inhibitory effect of two routinely used protein staining dyes viz Coomassie Brilliant blue G (CBBG) and Coomassie Brilliant blue R (CBBR) employing several biophysical and cell based methods. Our results showed that both the dyes not only efficiently inhibit fibrillisation but also disrupt existing fibrils. Nonetheless, only CBBR prevented the appearance of A11 epitopes which are marker of toxicity. Moreover, CBBR was also able to stall fibrillisation of A53T mutant α-synuclein and reduce associated neurotoxicity. This study thus reports the potential of CBBR as a therapeutic molecule.

Anti-Parkinsonian L-Dopa can also act as anti-systemic amyloidosis-A mechanistic exploration.

In spite of the fact that amyloid related neurodegenerative illnesses and non-neuropathic systemic amyloidosis have allured the research endeavors, as no cure has been announced yet apart from symptomatic treatment. Therapeutic agents which can reduce or disaggregate those toxic oligomers and fibrillar species have been studied with more compounds are on their way. The current research work describes comprehensive biophysical, computational and microscopic studies which reveal that L-3, 4-dihydroxyphenylalanine (L-Dopa) have indisputable efficacy to hinder the heat induced amyloid fibrillation of the human lysozyme (HL) and also preserve the fibril disaggregating potential. The IC50 value of L-Dopa is calculated to be 63.0±0.09µM. L-Dopa intervenes in the process of amyloid fibrillogenesis through hydrophobic interaction and hydrogen bond formation with the amino acid residues found in the amyloid fibril forming prone region of HL as clarified by molecular simulation data. L-Dopa also disaggregates the mature amyloid fibrils into some unorganized species and the DC50 value was estimated to be 19.95±0.063µM. Hence, L-Dopa and related compounds can act as effective inhibitors in the therapeutic development to combat systemic amyloidosis.