The canonical Wnt/β-catenin pathway is a highly conserved signaling cascade that plays critical roles during embryogenesis. Wnt ligands regulate axonal extension, growth cone guidance and synaptogenesis throughout the developing central nervous system (CNS). Recently, studies in mammalian and fish model systems have demonstrated that Wnt/β-catenin signaling also promotes axonal regeneration in the adult optic nerve and spinal cord after injury, raising the possibility that Wnt could be developed as a therapeutic strategy. In this review, we summarize experimental evidence that reveals novel roles for Wnt signaling in the injured CNS, and discuss possible mechanisms by which Wnt ligands could overcome molecular barriers inhibiting axonal growth to promote regeneration. A central challenge in the neuroscience field is developing therapeutic strategies that induce robust axonal regeneration. Although adult axons have the capacity to respond to axonal guidance molecules after injury, there are several major obstacles for axonal growth, including extensive neuronal death, glial scars at the injury site, and lack of axonal guidance signals. Research in rodents demonstrated that activation of Wnt/β-catenin signaling in retinal neurons and radial glia induced neuronal survival and axonal growth, but that activation within reactive glia at the injury site promoted proliferation and glial scar formation. Studies in zebrafish spinal cord injury models confirm an axonal regenerative role for Wnt/β-catenin signaling and identified the cell types responsible. Additionally, in vitro and in vivo studies demonstrated that Wnt induces axonal and neurite growth through transcription-dependent effects of its central mediator β-catenin, potentially by inducing regeneration-promoting genes. Canonical Wnt signaling may also function through transcription-independent interactions of β-catenin with cytoskeletal elements, which could stabilize growing axons and control growth cone movement. Therefore, these studies suggest that Wnt-induced pathways responsible for regulating axonal growth during embryogenesis could be repurposed to promote axonal growth after injury.

No abstract

Background Conjunctival lymphoma, conjunctival amyloidosis and benign reactive lymphoid hyperplasia (BRLH) are conditions that often have a similar appearance on the ocular surface. The use of high resolution anterior segment optical coherence tomography (HR-OCT) enables clinicians to evaluate distinctive differences in tissue morphology and cellular patterns in various ocular surface conditions. In this study, we characterize the morphological differences seen in conjunctival lymphoma, conjunctival amyloidosis and BRLH on HR-OCT imaging. Methods A retrospective chart review was performed of patients with biopsy proven conjunctival lymphoma, conjunctival amyloidosis and BRLH between 2012 and 2019 at the Bascom Palmer Eye Institute. Patients were excluded if HR-OCT imaging was not performed on initial presentation. Results Thirty-four total eyes of 27 patients were identified. Twenty eyes had conjunctival lymphoma (16 patients), 8 eyes had conjunctival amyloidosis (6 patients) and 6 eyes had BRLH (5 patients). All conditions appeared clinically as pink, red or yellow subepithelial lesions but had different features on HR-OCT. In lymphoma, HR-OCT images typically showed homogenous, dark subepithelial lesions with smooth borders, containing monomorphic dot-like infiltrates. HR-OCT images of amyloidosis typically showed heterogeneous, dark lesions with irregular borders, often containing hyperreflective linear infiltrates. HR-OCT images of BRLH showed variable infiltration of the subepithelial tissue, at times with homogenous lesions containing dot-like infiltrates like lymphoma and other times with more hyperreflective, subepithelial tissue. Flow cytometry and gene rearrangement was needed for final differentiation between BRLH and lymphoma lesions. Conclusions Distinctive features on HR-OCT of conjunctival lymphoma, conjunctival amyloidosis and BRLH can help characterize these lesions beyond what is apparent with the clinical examination. Future studies can further validate this technology’s use with more subtle and challenging lesions.

No abstract

Silicone-based compounds are commonly used in many medical applications, such as coatings for needles and syringes. Foreign body granulomas are a well-recognized complication of silicone exposure; however, they may be challenging to identify without a clear history. A 61-year-old female patient without prior history of periocular injections, filler, or surgery presented to our oculoplastic clinic with multiple periocular lesions. The patient subsequently underwent excisional biopsy of two prominent lesions, which were identified as granulomas on pathology. Further questioning revealed the cause to be facial acupuncture performed decades prior, and a subsequent targeted exam identified additional lesions at other needling sites. A third lesion was subsequently excised, and there was no recurrence at the last follow-up 3 months postsurgery. Acupuncture is an increasingly common but underrecognized source of silicone exposure and can present up to several decades after exposure as a chronic granulomatous response in a characteristic multifocal pattern.