Cytomegalovirus immunoglobulin therapy for CMV retinitis post hematopoietic stem cell transplantation.

PURPOSE: To report a case of cytomegalovirus (CMV) retinitis complicated with ganciclovir-related myelosuppression, which was successfully managed with intravenous (IV) ganciclovir and CMV immunoglobulin (CMVIG) therapy. METHODS: Observational case report. RESULTS: A 51-year-old male with follicular type non-Hodgkin lymphoma post hematopoietic stem cell transplantation (HSCT) developed vision-threatening retinitis. polymerase chain reaction (PCR) of the aqueous humour showed positive for CMV. Despite myelosuppression occurred during IV ganciclovir therapy, the retinitis resolved and intraocular CMV viral load significantly improved after CMVIG therapy. CONCLUSION: Combined IV ganciclovir treatment and CMVIG therapy can significantly improve visual outcome and reduce intraocular CMV viral load in vision-threatening CMV retinitis.

Spontaneous Closure of Cyclodialysis Cleft in a Case of Normal-Tension Glaucoma Post Ab-Interno Trabeculotomy.

A cyclodialysis cleft (CDC) is the detachment of longitudinal ciliary muscle from scleral spur, causing an unusual communication between anterior chamber and suprachoroidal space, resulting in possible hypotony. We report a case of a 63-year-old woman with normal-tension glaucoma (NTG), who developed a shallow anterior chamber with relatively low intraocular pressure (IOP, 6-8 mmHg) after combined ab-interno trabeculotomy and phacoemulsification. Her vision reached good (20/20) with the mild myopic shift. After detecting subtle signs of clinical hypotony, CDC was confirmed and monitored using anterior segment optical coherence tomography. Five months after surgery, she encountered an episode of eye pain, with transient IOP elevation and deepening of the anterior chamber. Spontaneous closure of CDC was suspected and confirmed gonioscopically. To the best of our knowledge, this is the first case to describe the clinical course of spontaneous CDC closure in a patient with NTG after ab-interno trabeculotomy. It is advisable to inform the patient about potential IOP spike after spontaneous closure once CDC is diagnosed.

BIK ubiquitination by the E3 ligase Cul5-ASB11 determines cell fate during cellular stress.

The BH3-only pro-apoptotic protein BIK is regulated by the ubiquitin-proteasome system. However, the mechanism of this regulation and its physiological functions remain elusive. Here, we identify Cul5-ASB11 as the E3 ligase targeting BIK for ubiquitination and degradation. ER stress leads to the activation of ASB11 by XBP1s during the adaptive phase of the unfolded protein response, which stimulates BIK ubiquitination, interaction with p97/VCP, and proteolysis. This mechanism of BIK degradation contributes to ER stress adaptation by promoting cell survival. Conversely, genotoxic agents down-regulate this IRE1α-XBP1s-ASB11 axis and stabilize BIK, which contributes in part to the apoptotic response to DNA damage. We show that blockade of this BIK degradation pathway by an IRE1α inhibitor can stabilize a BIK active mutant and increase its anti-tumor activity. Our study reveals that different cellular stresses regulate BIK ubiquitination by ASB11 in opposing directions, which determines whether or not cells survive, and that blocking BIK degradation has the potential to be used as an anti-cancer strategy.