Neurovascular injury associated non-apoptotic endothelial caspase-9 and astroglial caspase-9 mediate inflammation and contrast sensitivity decline

Lena SchadockLatest News

Neurovascular injury, such as retinal vein occlusion, triggers expression of endothelial caspase-9 (EC Casp9). EC Casp9 induces pathological changes, including retinal edema, capillary ischemia, and neurodegeneration. One of the behavioral consequences is decline of contrast sensitivity, as shown with our OptoDrum. This paper gives new mechanistic insights into EC Casp9 action.

B cell-dependent EAE induces visual deficits in the mouse with similarities to human autoimmune demyelinating diseases

Muriel Haag

The experimental autoimmune encephalomyelitis (EAE) mouse model is commonly used to study visual impairments associated with autoimmune demyelinating diseases. EAE is classically induced by immunization with the peptide MOG35-55. This mouse model lacks certain characteristics of analog diseases in humans, in particular the participation of B-cells in the immune response. Joly et al characterize the effects of immunization with a different peptide, bMOG, and find that these mice show hallmarks of common human diseases, such as multiple sclerosis and neuromyelitis optica. This new mouse model therefore offers new avenues to test protective or restorative ophthalmic treatments.

Systemic Treatment with Pioglitazone Reverses Vision Loss in Preclinical Glaucoma Models

Muriel Haag

In two mouse models of Glaucoma, Zeng et al show that Pioglitazone, given orally, can reduce or even reverse vision loss. Pioglitazone reduces inflammatory responses. The positive effects could be observed even with continued elevation of intraocular pressure, suggesting that the neuroinflammation experienced during Glaucoma may be more harmful than the elevated pressure.

TNF-α stimulation enhances the neuroprotective effects of gingival MSCs derived exosomes in retinal ischemia-reperfusion injury via the MEG3/miR-21a-5p axis

Muriel Haag

Exosomes are small vesicles enclosed by a single outer membrane secreted from cells, ranging from 30 to 200 nm in diameter, containing messenger RNAs, non-coding RNAs, proteins, and biological factors, and they may play a cru-cial role in intercellular communication. Exosomes have been identified as potential therapeutic methods and drug delivery tools. Exosomes derived from mesenchymal stem cells (MSCs) have been investigated in disorders such as stroke, corneal diseases, and liver diseases, but not yet in an acute glaucoma model, such as the ischemia-reperfusion model in the eye. Yu et al show that exosomes from MSCs have strong neuroprotective effects which is even better when the MSCs had been stimulated with TNF-α, and they identify the underlying signaling pathway. Their findings my pave the way for a new cell-free therapeutic approach for glaucoma.

Gain-of-function mutations in ALPK1 cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome

Muriel Haag

In a large study, spanning identification of patient cohorts, characterization of those patients’ phenotypes, genetic analysis, generation and characterization of animal models, Kozycki et al show that ROSAH syndrome (cause by mutations in the ALPK1 gene) is an autoinflammatory disease with a large range of consequences. They show that treatment with anti-inflammatory drugs is successful. The newly generated animal model only partially replicated the human phenotypes. For example, the mice did not have visual deficits and showed no signs of retinal degeneration.

Noninvasive Ophthalmic Imaging Measures Retinal Degeneration and Vision Deficits in Ndufs4−/− Mouse Model of Mitochondrial Complex I Deficiency

Muriel Haag

Mitochondrial complex I disorders are a heterogeneous group of rare inherited diseases caused by mutations affecting proteins in the mitochondrial electron transport chain. Neurological and ophthalmic pathologies are common to many forms of complex I deficiency, due to the high energy demands of central nervous system tissues. Avrutsky et al characterized one such mouse model, carrying a mutation in Ndufs4 (NADH:ubiquinone oxidoreductase Fe-S pro-tein 4), which shows fast retinal degeneration within only a few weeks. They show that a range of non-invasive techniques (OCT for structural changes, ERG for electrophysiological properties, and OMR with our OptoDrum for behavioral assessment) can capture relevant measures of disease progression.