Airway and alveolar fluid clearance is mainly governed by vectorial salt movement via apically located rate-limiting Na + channels (ENaC) and basolateral Na + /K + -ATPases. ENaC is regulated by a spectrum of protein kinases, i.e. protein kinase A (PKA), C (PKC), and G (PKG). However, the molecular mechanisms for the regulation of ENaC by cGMP/PKG remain to be elucidated. In the present study, we studied the pharmacological responses of native epithelial Na + channels in human Clara cells and human αβγδ ENaCs expressed in oocytes to cGMP. 8-pCPT-cGMP increased amiloride-sensitive short-circuit current (I sc ) across H441 monolayers and heterologously expressed αβγδ ENaC activity in a dose-dependent manner. Similarly, 8-pCPT-cGMP (a PKGII activator) but not 8-Br-cGMP (a PKGI activator) increased amiloride-sensitive whole cell currents in H441 cells in the presence of CFTRinh-172 and diltiazem. In all cases, the cGMP-activated Na + channel activity was inhibited by Rp-8-pCPT-cGMP, a specific PKGII inhibitor. This was substantiated by the evidence that PKGII was the sole isoform expressed in H441 cells at the protein level. Importantly, intratracheal instillation of 8-pCPT-cGMP in BALB/c mice increased amiloride-sensitive alveolar fluid clearance by ∼30%, consistent with the in vitro results. We therefore conclude that PKGII is an activator of lung epithelial Na + channels, which may expedite the resolution of oedematous fluid in alveolar sacs.

Glaucoma is the second leading cause for blindness worldwide. It is mainly caused by glaucomatous optic neuropathy (GON) characterized by retinal ganglion cell loss, which leads to visual field defect and blindness. Up to now, the main purpose of antiglaucomatous therapies has been to lower intraocular pressure (IOP) through surgeries and medications. However, it has been found that progressive GON is still present in some patients with effective IOP decrease. Therefore, risk factors other than IOP elevation, like neurotrophin deprivation and excitotoxicity, contribute to progressive GON. Novel approaches of neuroprotection may be more effective for preserving the function of the optic nerve.

Rationale:Axenfeld–Rieger syndrome (ARS) is a rare autosomal dominant disorder with ocular anterior segment dysgenesis and systemic anomalies.Patient concerns:A 28-year-old Chinese Han female was referred to Beijing Tongren Eye Center for progressive decrease of the visual acuity on her right eye in the past month.Diagnoses:The patient was diagnosed as ARS with retinal detachment based on series of ophthalmic examinations performed.Interventions:A pars plana vitrectomy was performed to manage the retinal detachment.Outcomes:Her best-corrected visual acuity was slightly improved after surgery.Lessons:ARS is a developmental defect of ocular anterior segment with various clinical manifestations which might cause misdiagnosis.

No abstract