Mller Cells in the Healthy and Diseased Retina

Mller glial cells ensheath all retinal neurons in vertebrate retinae. There are a multitude of functional interactions between neurons and Mller cells, including delivery of the light stimuli to the photoreceptor cells in the inverted vertebrate retina, a 'metabolic symbiosis' with the neurons, and the processing of visual information. Mller cells are also responsible for the maintenance of the homeostasis of the retinal extracellular milieu (ions, water, neurotransmitter molecules, and pH). In vascularized retinae, Mller cells may also be involved in the control of angiogenesis, and the regulation of retinal blood flow. Virtually every disease of the retina is associated with a reactive Mller cell gliosis which, on the one hand, supports the survival of retinal neurons but, on the other hand, may accelerate the progress of neuronal degeneration:

Mller cells protect neurons via a release of neurotrophic factors. However, gliotic Mller cells display a dysregulation of various neuron-supportive functions. This contributes to a disturbance of retinal glutamate metabolism and ion homeostasis, and causes the development of retinal edema and neuronal cell death. Moreover, there are diseases evoking a primary Mller cell insufficiency, such as hepatic retinopathy and certain forms of glaucoma. Any impairment of supportive functions of Mller cells, primary or secondary, must cause and/or aggravate a dysfunction and loss of neurons, by increasing the susceptibility of neurons to stressful stimuli in the diseased retina.

Mller cells may be used in the future for novel therapeutic strategies to protect neurons against apoptosis (i.e. somatic gene therapy), or to differentiate retinal neurons from Mller/stem cells. Meanwhile, a proper understanding of the gliotic responses of Mller cells in the diseased retina, and of their protective vs. detrimental effects, is essential for the development of efficient therapeutic strategies that use and stimulate the neuron-supportive/-protective - and prevent the destructive - mechanisms of gliosis.