Human CD34 fibrocytes, circulating monocyte lineage progenitor cells, have recently been implicated in thyroid-associated ophthalmopathy (TAO), the ocular manifestation of Graves' disease (GD). Fibrocytes express constitutive MHC class II (MHC-2) and, surprisingly, thyroglobulin (Tg) and functional thyrotropin (TSH) receptor (TSHR). Underlying expression of these thyroid proteins is the autoimmune regulator protein (AIRE). Fibrocytes respond robustly to TSH and thyroid-stimulating Igs by generating extremely high levels of inflammatory cytokines, such as IL-6. In TAO, they appear to infiltrate the orbit, where they transition to CD34 orbital fibroblasts (OF). There, they coexist with CD34 OF as a mixed fibroblast population (GD-OF). In contrast to fibrocytes, GD-OF express vanishingly low levels of MHC-2, Tg, TSHR, and AIRE. Further, the amplitude of IL-6 induction by TSH in GD-OF is substantially lower. The molecular basis for this divergence between fibrocytes and CD34 OF remains uncertain. In this article, we report that Slit2, an axon guidance glycoprotein, is constitutively expressed by the CD34 OF subset of GD-OF. Culture conditioned medium (CM) generated by incubating with GD-OF and CD34 OF substantially reduces levels of MHC-2, Tg, TSHR, and AIRE in fibrocytes. Expression can be restored by specifically depleting CM of Slit2. The effects of CD34 OF CM are mimicked by recombinant human Slit2. TSH induces Slit2 levels in GD-OF by enhancing both Slit2 gene transcription and mRNA stability. These findings suggest that Slit2 represents a TSH-inducible factor within the TAO orbit that can modulate the inflammatory phenotype of CD34 OF and therefore may determine the activity and severity of the disease.
Information and communication technology has rapidly reached diverse aspects of modern life, including medicine and health-related matters. Aiming to improve teaching, research, and health care delivery for geographic or economic reasons, telemedicine is an ascending trend. Teleophthalmology might be one of the most challenging applications of telemedicine given its need for standardized and high definition digital images. However, technological advances are enhancing information transmission continuously and expanding the potential of teleophthalmology. In this review, we investigate the evolution and current status of teleophthalmology, describe its use in different areas, and explore its applicability. Although teleophthalmology is not a replacement for traditional eye care and still faces challenges for adequate implementation, it represents an effective care delivery method, facilitating appropriate and timely distribution of service especially in remote and/or underdeveloped regions.
Thyroid-associated ophthalmopathy (TAO) is a condition associated with a wide spectrum of ocular changes, usually in the context of the autoimmune syndrome, Graves’ disease. In this topical review, we attempted to provide a roadmap of the recent advances in current understanding the pathogenesis of TAO, important aspects of its clinical presentation, its impact on the ocular surface, describe the tissue abnormalities frequently encountered, and describe how TAO is managed today. We also briefly review how increased understanding of the disease should culminate in improved therapies for patients with this vexing condition.
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