How night vision is maintained during retinal degenerative disease
New findings in mice could inform novel treatment strategies for diseases
that cause blindness

Date:
September 22, 2020
Source:
eLife
Summary:
New insight on how people with retinal degenerative disease can
maintain their night vision for a relatively long period of time
has just been published.



FULL STORY ==========================================================================
New insight on how people with retinal degenerative disease can maintain
their night vision for a relatively long period of time has been published today in the open-access eLife journal.


==========================================================================
The study in mice suggests that second-order neurons in the retina,
which relay visual signals to the retinal ganglion cells that project
into the brain, maintain their activity in response to photoreceptor degeneration to resist visual decline -- a process known as homeostatic plasticity. Rod photoreceptors are the cells responsible for the most
sensitive aspects of our vision, allowing us to see at night, but can
be lost during retinal degenerative disease.

The new findings pave the way for further research to understand how
our eyes and other sensory systems respond and adapt to potentially compromising changes throughout life.

"Neuronal plasticity of the inner retina has previously been seen to
occur in response to photoreceptor degeneration, but this process has
been mostly considered maladaptive rather than homeostatic in nature,"
explains co-first author Henri Leinonen, a postdoctoral researcher at
the University of California, Irvine, US. "Our study was conducted at
a relatively early stage of disease progression, while most previous
studies focused on severe disease stages, which may account for the discrepancy. Very recently, several studies using triggered photoreceptor
loss models have shown adaptive responses in bipolar cells -- cells that connect the outer and inner retina. But whether such adaptation occurs
during progressive photoreceptor degenerative disease, and whether
it helps to maintain visual behaviour, was unknown." To address this
question, Leinonen and colleagues studied a mouse model of retinitis pigmentosa. This is the name given to a group of related genetic disorders caused by the P23H mutation in rhodopsin, a protein that enables us to
see in low-light conditions. Retinitis pigmentosa causes the breakdown
and loss of rod-shaped photoreceptor cells in the retina, leading to difficulties seeing at night.

The team combined whole-retinal RNA-sequencing, electrophysiology and behavioral experiments in both healthy mice and those with retinitis
pigmentosa as the disease progressed. Their experiments showed that
the degeneration of rod photoreceptors triggers genomic changes that
involve robust compensatory molecular changes in the retina and increases
in electrical signalling between rod photoreceptors and rod bipolar
cells. These changes were associated with well-maintained behavioural
night vision despite the loss of over half of the rod photoreceptor
cells in mice with retinitis pigmentosa.

"This mechanism may explain why patients with inherited retinal diseases
can maintain their normal vision until the disease reaches a relatively advanced state," says co-first author Nguyen Pham, Graduate Research
Assistant at the John A. Moran Eye Center, University of Utah Health,
Salt Lake City, US. "It could also inspire novel treatment strategies for diseases that lead to blindness." "Our results suggest retinal adaptation
as the driver of persistent visual function during photoreceptor
degenerative disease," concludes senior author Frans Vinberg, PhD,
Assistant Professor at the John A. Moran Eye Center, University of
Utah Health. "Additional research is now needed to discover the exact homeostatic plasticity mechanisms that promote cellular signalling and
visual function. This could help inform the development of potential
new interventions to enhance homeostatic plasticity when needed."

========================================================================== Story Source: Materials provided by eLife. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Henri Leinonen, Nguyen C Pham, Taylor Boyd, Johanes Santoso,
Krzysztof
Palczewski, Frans Vinberg. Homeostatic plasticity in the retina
is associated with maintenance of night vision during retinal
degenerative disease. eLife, 2020; 9 DOI: 10.7554/eLife.59422 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200922135726.htm

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