A case report of retinal dystrophy in patients with PACS1 syndrome.

PACS1 syndrome, also referred to as Schuurs-Hoeijmakers syndrome, is a multisystemic developmental disorder caused by a specific pathogenic variant in the PACS1 (phosphofurin acidic cluster sorting protein 1) gene. Ocular findings in PACS1 syndrome are known to include iris, retina, optic nerve coloboma, myopia, nystagmus, and strabismus. Here, we present the cases of two patients referred to the University of Wisconsin-Madison Department of Ophthalmology and Visual Sciences for ocular evaluation. The first patient is a 14-month-old female who, at 3 months of age, was found to have a depressed rod and cone response on electroretinogram (ERG), consistent with possible retinal dystrophy (RD). This feature has not been previously described in PACS1 syndrome and joins a growing list of calls for expanding the PACS1 phenotype. The second case illustrates a 5-year-old male referred for ocular screening after diagnosing PACS1 syndrome and underwent ERG without abnormal findings. These cases demonstrate the significant variability in the ophthalmic presentation of PACS1 syndrome and the need for early screening. These novel findings may have implications in understanding the mechanism of the PACS1 protein and its role in retinal ciliary phototransduction in photoreceptors.

Therapeutic Outcomes of Non-Infectious Scleritis Treated with Tumor Necrosis Factor-Alpha Inhibitors.

PURPOSE: We determine the efficacy of tumor necrosis factor-α (TNF) inhibitors in establishing scleritis quiescence. METHODS: We conducted a multicenter retrospective chart review of patients with non-infectious scleritis treated with a TNF inhibitor for at least 6 months. The primary endpoint was scleritis quiescence at 6 months. Secondary endpoints included scleritis quiescence at 12 months, TNF inhibitor effects on concurrent doses of systemic corticosteroids and visual acuity outcomes at 6 and 12 months. RESULTS: At 6 months, 82.2% (37/45) of subjects obtained scleritis quiescence with TNF inhibition. At 12 months, 76.2% (32/42) of subjects remained quiescent. Baseline daily corticosteroid use (21.5 ± 21.6 mg) decreased to 5.4 ± 8.3 mg by 6 months (p < 0.0001) and 2.8 ± 6.1 mg by 12 months (p < 0.001). There was no significant difference between the baseline and 6-month BCVA (p = 0.52). CONCLUSIONS: TNF inhibitors are an effective scleritis therapy with significant systemic corticosteroid sparing effect.

Retractable Urology Three-Pronged Grasping Forceps for Removal of Large, Non-Magnetic Intraocular Foreign Bodies.

PURPOSE: To demonstrate the use of urology retractable three-pronged grasping forceps in the removal of a large, round, and non-magnetic intraocular foreign body (IOFB) that was difficult to remove with other surgical instruments. METHODS: Extraction of a 3.0 mm lead shot pellet embedded in vitreous hemorrhage was attempted with multiple surgical instruments including an intraocular magnet, IOFB forceps, and two tools designed for urology stone removal: a three-pronged grasping forceps and a nitinol basket extractor. RESULTS: Due to the round and smooth surface, large size, and non-magnetic nature of the IOFB, extraction was challenging and failed with multiple other surgical instruments. The wide and secure grasp of the grasping forceps allowed for swift IOFB extraction without iatrogenic injury to the retina. CONCLUSION: The grasping forceps offer an effective and safe method for removal of large, round, and non-magnetic IOFBs.

Compartmentalization of HP1 Proteins in Pluripotency Acquisition and Maintenance.

The heterochromatin protein 1 (HP1) family is involved in various functions with maintenance of chromatin structure. During murine somatic cell reprogramming, we find that early depletion of HP1γ reduces the generation of induced pluripotent stem cells, while late depletion enhances the process, with a concomitant change from a centromeric to nucleoplasmic localization and elongation-associated histone H3.3 enrichment. Depletion of heterochromatin anchoring protein SENP7 increased reprogramming efficiency to a similar extent as HP1γ, indicating the importance of HP1γ release from chromatin for pluripotency acquisition. HP1γ interacted with OCT4 and DPPA4 in HP1α and HP1ß knockouts and in H3K9 methylation depleted H3K9M embryonic stem cell (ESC) lines. HP1α and HP1γ complexes in ESCs differed in association with histones, the histone chaperone CAF1 complex, and specific components of chromatin-modifying complexes such as DPY30, implying distinct functional contributions. Taken together, our results reveal the complex contribution of the HP1 proteins to pluripotency.

17beta-estradiol modulation of angiotensin II-stimulated response in cardiac fibroblasts.

The ovarian hormone, 17beta-estradiol, has been suggested to play an important role in gender-specific differences in cardiovascular diseases. One possible cardioprotective mechanism involves the interaction between 17beta-estradiol and the renin-angiotensin system. Previous studies demonstrated that fibroblast function and gene expression are regulated by biochemical factors including growth factors, hormones, and cytokines, but little is known regarding the integration of these diverse signals. Therefore, the purpose of this study was to determine the ability of 17beta-estradiol to modulate angiotensin II (AngII) effects on integrin-induced collagen gel contraction, matrix metalloproteinase (MMP) activity and expression, and signal transduction pathways in isolated neonatal cardiac fibroblasts. 17beta-estradiol significantly attenuated AngII-stimulated collagen gel contraction and significantly diminished the effect of AngII on the expression of beta1 and not alpha1integrins. Active MMP-2 levels were decreased by AngII and addition of 17beta-estradiol resulted in further reductions. Relative MMP-2 mRNA levels showed essentially identical patterns to protein levels. 17beta-estradiol pretreatment increased AngII-mediated mitogen-activated protein (MAP) kinase p42/44 activation and slightly decreased p38 activation compared to non-pretreated fibroblasts. Simultaneous addition of 17beta-estradiol and AngII had little to no effect on AngII activation of p42/44 or p38 MAP kinase. The current studies demonstrate the inhibitory role of estrogen on AngII-induced fibroblast-mediated ECM remodeling, gene expression, and signal transduction. These studies begin to elucidate the mechanisms of estrogen effects on myocardial remodeling and function.