Emerging glaucoma treatments: are we seeing an improvement in adherence?

Introduction: Non-adherence to glaucoma medication and poor follow-up is a global health concern. Areas covered: Glaucoma remains one of the largest causes of irreversible blindness worldwide. Traditional treatment guidelines suggest topical eye drop medication as first line therapy followed by addition of supplementary medications before proceeding to more invasive glaucoma surgeries. Unfortunately, poor glaucoma self-management remains high, leading to disease progression and blindness. Recent advancements in the field of pharmacotherapies, surgeries, and behavioral approaches have taken aim at increasing support for glaucoma self-management. We review the current and emerging approaches towards glaucoma management, with the exception of bleb-based surgical approaches, to investigate if they have had an impact on adherence. Literature searches were conducted via MEDLINE (PubMed), Embase (Elsevier), Cochrane Library (Wiley), and Preprints from January 1st, 2018, to January 26th, 2023. Expert opinion: The ability to offer patients a multitude of choices enables patients to tailor their glaucoma treatment to their values and lifestyle. Offering personalized patient education and coaching to support chronic glaucoma self-management would better enable patient engagement in whichever treatment path is chosen. Currently, literature regarding the impact of these new advancements on treatment engagement is lacking; this field is ripe for additional intervention and assessment.

Penaeid shrimp brachyury: sequence analysis and expression during gastrulation.

Gastrulation occurs by a variety of morphogenetic movements, often correlated with diverse expression of the T-box transcription factor Brachyury (Bra). Bra may be expressed in ectoderm, mesoderm, or endoderm, but its role in cell fate specification or regulation of gastrulation movements has not been studied in the development of crustaceans. Penaeid shrimp (Decapoda: Dendrobranchiata: Penaeidae) develop by complete cleavage and gastrulation by invagination to a free-swimming nauplius larva. Penaeid gastrulation diverges from other decapods and from insects, occurring early at a low cell number with the formation of a radial invagination. Toward a better understanding of gastrulation movements in penaeid shrimp, bra was identified from newly available penaeid shrimp genomes and transcriptomes of Litopenaeus vannamei, Marsupenaeus japonicus, and Penaeus monodon. Additional bra homologs were obtained from the outgroups Sicyonia ingentis (Decapoda: Dendrobranchiata: Sicyoniidae) and the caridean shrimp Caridina multidentata (Decapoda: Pleocymata). The genes encoded penaeid shrimp Bra proteins of 551-552 amino acids, containing the highly conserved T-box DNA-binding region. The N-terminal Smad1-binding domain, conserved in most animals, was absent in shrimp Bra. The R1 repressor domain was the best conserved of the C-terminal regulatory domains, which were widely divergent compared to other species. The penaeid shrimp bra gene consisted of six exons, with splice sites conserved with other phyla across the animal kingdom. Real-time qPCR and FPKM analysis showed that shrimp bra mRNA was strongly expressed during gastrulation. These findings begin to address the evolution of gastrulation in shrimp at the molecular level.

Regulation of Gonad Morphogenesis in Drosophila melanogaster by BTB Family Transcription Factors.

During embryogenesis, primordial germ cells (PGCs) and somatic gonadal precursor cells (SGPs) migrate and coalesce to form the early gonad. A failure of the PGCs and SGPs to form a gonad with the proper architecture not only affects germ cell development, but can also lead to infertility. Therefore, it is critical to identify the molecular mechanisms that function within both the PGCs and SGPs to promote gonad morphogenesis. We have characterized the phenotypes of two genes, longitudinals lacking (lola) and ribbon (rib), that are required for the coalescence and compaction of the embryonic gonad in Drosophila melanogaster. rib and lola are expressed in the SGPs of the developing gonad, and genetic interaction analysis suggests these proteins cooperate to regulate gonad development. Both genes encode proteins with DNA binding motifs and a conserved protein-protein interaction domain, known as the Broad complex, Tramtrack, Bric-à-brac (BTB) domain. Through molecular modeling and yeast-two hybrid studies, we demonstrate that Rib and Lola homo- and heterodimerize via their BTB domains. In addition, analysis of the colocalization of Rib and Lola with marks of transcriptional activation and repression on polytene chromosomes reveals that Rib and Lola colocalize with both repressive and activating marks and with each other. While previous studies have identified Rib and Lola targets in other tissues, we find that Rib and Lola are likely to function via different downstream targets in the gonad. These results suggest that Rib and Lola act as dual-function transcription factors to cooperatively regulate embryonic gonad morphogenesis.