Elevated granulocyte colony stimulating factor (CSF) causes cerebellar deficits and anxiety in a model of CSF-1 receptor related leukodystrophy.

Colony stimulating factor (CSF) receptor-1 (CSF-1R)-related leukoencephalopathy (CRL) is an adult-onset, demyelinating and neurodegenerative disease caused by autosomal dominant mutations in CSF1R, modeled by the Csf1r mouse. The expression of Csf2, encoding granulocyte-macrophage CSF (GM-CSF) and of Csf3, encoding granulocyte CSF (G-CSF), are elevated in both mouse and human CRL brains. While monoallelic targeting of Csf2 has been shown to attenuate many behavioral and histological deficits of Csf1r mice, including cognitive dysfunction and demyelination, the contribution of Csf3 has not been explored.

Scleral Tonometry Precision During Scleral Lens Wear: A Pilot Study.

Purpose: To evaluate the reproducibility, and therefore the utility, of using traditional tonometry devices for measuring intraocular pressure (IOP), while a prosthetic replacement of the ocular surface ecosystem device (PD) or scleral lens is applied to the eye.

Patients And Methods: Twenty subjects (40 eyes) with keratoconus were enrolled. With PD applied, the first 10 consecutive patients had IOP measured multiple times with a handheld tonometer (Tono-Pen AVIA, Reichert, Depew, NY) on the superotemporal sclera 1 mm posterior to the PD edge.

Microglial reduction of colony stimulating factor-1 receptor expression is sufficient to confer adult onset leukodystrophy.

Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a dementia resulting from dominantly inherited CSF1R inactivating mutations. The Csf1r mouse mimics ALSP symptoms and pathology. Csf1r is mainly expressed in microglia, but also in cortical layer V neurons that are gradually lost in Csf1r+/- mice with age.

Microglial Homeostasis Requires Balanced CSF-1/CSF-2 Receptor Signaling.

CSF-1R haploinsufficiency causes adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). Previous studies in the Csf1r mouse model of ALSP hypothesized a central role of elevated cerebral Csf2 expression. Here, we show that monoallelic deletion of Csf2 rescues most behavioral deficits and histopathological changes in Csf1r mice by preventing microgliosis and eliminating most microglial transcriptomic alterations, including those indicative of oxidative stress and demyelination.