Prostaglandin-Induced Macular Hole: A Brief Report.

This case series reports on two patients who developed macular holes while on prostaglandin analogs (PGA) therapy. The first case involves a 63-year-old woman with a history of a macular hole of the left eye that had spontaneously closed. After starting PGA therapy for elevated intraocular pressure, cystoid macular edema formed, which resulted in reopening of the macular hole. The second case involves a 64-year-old man with primary open-angle glaucoma, on PGA therapy, with a newly diagnosed small macular hole of the right eye that closed after cessation of the PGA therapy. These cases demonstrate an association between prostaglandin analogs and the formation or reopening of full-thickness macular holes. [Ophthalmic Surg Lasers Imaging Retina 2024;55:112-115.].

ßII-Spectrin Is Required for Synaptic Positioning during Retinal Development.

Neural circuit assembly is a multistep process where synaptic partners are often born at distinct developmental stages, and yet they must find each other and form precise synaptic connections with one another. This developmental process often relies on late-born neurons extending their processes to the appropriate layer to find and make synaptic connections to their early-born targets. The molecular mechanism responsible for the integration of late-born neurons into an emerging neural circuit remains unclear. Here, we uncovered a new role for the cytoskeletal protein ßII-spectrin in properly positioning presynaptic and postsynaptic neurons to the developing synaptic layer. Loss of ßII-spectrin disrupts retinal lamination, leads to synaptic connectivity defects, and results in impaired visual function in both male and female mice. Together, these findings highlight a new function of ßII-spectrin in assembling neural circuits in the mouse outer retina.SIGNIFICANCE STATEMENT Neurons that assemble into a functional circuit are often integrated at different developmental time points. However, the molecular mechanism that guides the precise positioning of neuronal processes to the correct layer for synapse formation is relatively unknown. Here, we show a new role for the cytoskeletal scaffolding protein, ßII-spectrin in the developing retina. ßII-spectrin is required to position presynaptic and postsynaptic neurons to the nascent synaptic layer in the mouse outer retina. Loss of ßII-spectrin disrupts positioning of neuronal processes, alters synaptic connectivity, and impairs visual function.

Fluorogenic monomer activation for protein-initiated atom transfer radical polymerization.

Fluorogenic atom transfer radical polymerization (ATRP) directly detects initiator-dependent polymer formation, as initially non-fluorescent polycyclic aromatic probe monomers reveal visible fluorescence upon polymerization in real time. Advancement of this initial proof-of-concept toward biodetection applications requires both a more detailed mechanistic understanding of probe fluorescence activation, and the ability to initiate fluorogenic polymerization directly from a biomolecule surface. Here, we show that simple monomer hydrogenation, independent of polymerization, reveals probe fluorescence, supporting the critical role of covalent enone attachment in fluorogenic probe quenching and subsequent fluorescence activation. We next demonstrate bioorthogonal, protein-initiated fluorogenic ATRP by the surface conjugation and characterization of protein-initiator conjugates of a model protein, bovine serum albumin (BSA). Fluorogenic ATRP from initiator-modified protein allows for real-time visualization of polymer formation with negligible background fluorescence from unmodified BSA controls. We further probe the bioorthogonality of this fluorogenic ATRP assay by assessing polymer formation in a complex biological environment, spiked with fetal bovine serum. Taken together, we demonstrate the potential of aqueous fluorogenic ATRP as a robust, bioorthogonal method for biomolecular-initiated polymerization by real-time fluorescence activation.

Fluorogenic atom transfer radical polymerization in aqueous media as a strategy for detection.

The development of novel approaches to signal amplification in aqueous media could enable new diagnostic platforms for the detection of water-soluble analytes, including biomolecules. This paper describes a fluorogenic polymerization approach to amplify initiator signal by the detection of visible fluorescence upon polymerization in real-time. Fluorogenic monomers were synthesized and co-polymerized by atom transfer radical polymerization (ATRP) in water to reveal increasing polymer fluorescence as a function of both reaction time and initiator concentration. Optimization of the fluorogenic ATRP reaction conditions allowed for the quantitative detection of a small-molecule initiator as a model analyte over a broad linear concentration range (pM to mM). Raising the reaction temperature from 30 °C to 60 °C facilitated sensitive initiator detection at sub-picomolar concentrations in as little as 1 h of polymerization. This method was then applied to the detection of streptavidin as a model biological analyte by fluorogenic polymerization from a designed biotinylated ATRP initiator. Taken together, these studies represent the first example of a fluorogenic ATRP reaction and establish fluorogenic polymerization as a promising approach for the direct detection of aqueous analytes and biomolecular recognition events.