Clinical, histological and genetic findings in a donor with a clinical history of type 1 Autoimmune Polyendocrinopathy Syndrome.

PURPOSE: Autoimmune Polyendocrinopathy Syndrome (APS) is a rare condition caused by an autoimmune failure of two or more endocrine glands. In this case, we report the ocular findings and correlated histopathology from a human eye donor with a prior clinical history of Type 1 APS. OBSERVATIONS: The 23 year-old patient originally presented with blurred vision at the 20/125 level caused by papilledema of the right eye. Bilateral pigmentary changes in the peripheral retinal were also noted. The patient passed away due to electrolyte abnormalities related to autoimmune illness. Histopathology of the posterior segments documents that these pigmentary changes were caused by pigment deposition around inner retinal vessels with corresponding outer retina atrophy. Postmortem genetic sequence analyses revealed a homozygous R257X (C to T substitution) mutation within exon 6 of the AIRE gene. CONCLUSIONS AND IMPORTANCE: The retinal findings in Type 1 Autoimmune Polyendocrinopathy Syndrome resemble those observed in individuals with retinitis pigmentosa, suggesting that similar pathological processes occur in both.

Effect of longitudinal and torsional ultrasound on corneal endothelial cells: experimental study in rabbit eyes.

PURPOSE: To compare corneal endothelial damage from longitudinal and torsional ultrasound during phacoemulsification. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: 9 New Zealand white rabbits underwent bilateral surgery. After incision, the Intrepid Balanced Tip of the Centurion Ozil handpiece was inserted into the anterior chamber, and the following settings were used: 50 mL/min flow, 70 mm Hg intraocular pressure, 600 mm Hg vacuum, and 60% longitudinal (1 eye) or torsional (contralateral eye) ultrasound for 30 seconds. Cumulative dissipated energy (CDE) was noted. After euthanasia and enucleation, the corneas were removed, stained with trypan blue/alizarin red, and photographed (400× photographs from 5 specific areas and 1 overview photograph from each corneal button). The ImageJ program was used to evaluate cell damage and loss in the photographs obtained from each cornea. RESULTS: Cavitation bubbles around the phacoemulsification tip were generally observed in the longitudinal group. CDE was 17.4 ± 0.58 and 6.93 ± 0.15 in the longitudinal and torsional groups, respectively (P = .003). The percentage of intact cells was statistically higher in the torsional group (94.22% ± 5.99% vs 56.85% ± 22.29%), and the percentage of lost cells was statistically higher in the longitudinal group (42.10% ± 22.02% vs 4.97% ± 6.23%) (P = .003). This was observed in the analysis of the 400× photographs and the overview photographs. CONCLUSIONS: This study suggests that torsional ultrasound was associated with significantly less corneal endothelial cell damage than classical longitudinal tip motion, providing further insight on mechanisms of corneal endothelial damage during phacoemulsification.

Effect of phacoemulsification fluid flow on the corneal endothelium: experimental study in rabbit eyes.

PURPOSE: To quantify the damage to the corneal endothelium from the flow of a balanced salt solution during phacoemulsification. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah. DESIGN: Experimental study. METHODS: 12 New Zealand white rabbits received bilateral surgery. 6 eyes served as controls with no irrigation (incision only). In 18 eyes, the Intrepid Balanced tip of the Centurion Ozil (Alcon Laboratories, Inc.) handpiece was inserted into the anterior chamber for continuous irrigation at 50 mL/min with either 250 or 500 mL of balanced salt solution. After killing humanely and enucleation, the corneas were removed, stained with trypan blue-alizarin red, and photographed in a standardized manner (×400 photographs from 5 specific areas and 1 overview photograph from each corneal button). The ImageJ program was used to evaluate cell damage and loss in the photographs obtained from each cornea. RESULTS: Analysis of the ×400 photographs showed no statistically significant differences between control, 250 mL, and 500 mL groups in the percentage of intact, damaged, or lost cells (P = .896, .851, and .972 respectively). For the overview photographs, the differences in areas of intact and damaged cells among the groups were statistically significant, likely because of the peripheral areas of damage related to touches between the phacoemulsification tip and the endothelium during irrigation. CONCLUSIONS: The volume of balanced salt solution flow alone did not seem to be a major contributing source of endothelial cell damage and loss, providing further insight into mechanisms of corneal endothelium damage during phacoemulsification.

Clinical and histopathological findings in the dead bag syndrome.

PURPOSE: To describe the findings of a recently described syndrome, the dead bag syndrome, in which the capsular bag appears to be clear many years postoperatively, becoming diaphanous and floppy and unable to support the intraocular lens (IOL) within it. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah. DESIGN: Case series with clinicopathological correlation. METHODS: Of 10 cases suspected to represent a dead bag syndrome, 8 IOLs and 7 capsular bags were removed because of subluxation or dislocation. The 7 capsular bags available for analysis were fixed in formalin and submitted to histopathological examination (hematoxylin-eosin and Masson trichrome stains). The associated explanted IOLs in 5 cases were also examined microscopically. RESULTS: Histopathologic examination of the 7 capsular bags showed capsular thinning and/or splitting. Lens epithelial cells (LECs) were completely absent on 2 specimens, whereas the other 5 specimens had rare LECs on the inner surface of the capsule. Explanted IOLs were 3-piece silicone IOLs or single-piece hydrophobic acrylic IOLs. 1 IOL optic showed a small amount of granular pigment deposition, but the optics of the other 4 IOLs were unremarkable. CONCLUSIONS: In this syndrome, there seems to be an absence of secondary proliferation of LECs and fibrotic changes. The capsule shows some signs of degradation, such as thinning and/or splitting. Weakness of zonular attachments seems to be an associated finding, with subsequent in-the-bag IOL dislocation. Further studies are necessary to ascertain the etiology of this condition.

Enhanced expression and activity of Nox2 and Nox4 in the macula densa in ANG II-induced hypertensive mice.

NAD(P)H oxidase (Nox)2 and Nox4 are the isoforms of Nox expressed in the macula densa (MD). MD-derived superoxide (O2⁻), primarily generated by Nox2, is enhanced by acute ANG II stimulation. However, the effects of chronic elevations in ANG II during ANG II-induced hypertension on MD-derived O2⁻ are unknown. We infused a slow pressor dose of ANG II (600 ng·min⁻¹·kg⁻¹) for 2 wk in C57BL/6 mice and found that mean arterial pressure was elevated by 22.3 ± 3.4 mmHg (P < 0.01). We measured O2⁻ generation in isolated and perfused MDs and found that O2⁻ generation by the MD was increased from 9.4 ± 0.9 U/min in control mice to 34.7 ± 1.8 U/min in ANG II-induced hypertensive mice (P < 0.01). We stimulated MMDD1 cells, a MD-like cell line, with ANG II and found that O2⁻ generation increased from 921 ± 91 to 3,687 ± 183 U·min⁻¹·105 cells⁻¹, which was inhibited with apocynin, oxypurinol, or NS-398 by 46%, 14%, and 12%, respectively. We isolated MD cells using laser capture microdissection and measured mRNA levels of Nox. Nox2 and Nox4 levels increased by 3.7 ± 0.17- and 2.6 ± 0.15-fold in ANG II-infused mice compared with control mice. In MMDD1 cells treated with Nox2 or Nox4 small interfering (si)RNAs, ANG II-stimulated O2⁻ generation was blunted by 50% and 41%, respectively. In cells treated with p22(phox) siRNA, ANG II-stimulated O2⁻ generation was completely blocked. In conclusion, we found that a subpressor dose of ANG II enhances O2⁻ generation in the MD and that the sources of this O2⁻ are primarily Nox2 and Nox4.