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Immunosuppressive Treatment Can Alter Visual Performance in the Royal College of Surgeons Rat
Ann E Cooper1, Jang-Hyeon Cho2, Steven Menges2
11 William R. Pritchard Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California-Davis , Davis, California.
Purpose:
Immunosuppression is frequently employed to enhance survival of xenografted human cells as part of translational proof-of-concept studies. However, the potential effects of this treatment are easily overlooked.
Methods:
As part of baseline testing in the dark-eyed variant of the dystrophic Royal College of Surgeons (RCS) rat, we documented the time course of retinal degenerative changes versus Long Evans controls using bright field retinal imaging, fluorescein angiography, and histology and examined the impact of immunosuppression on visual function. Rats received either no treatment or systemic immunosuppression with oral cyclosporine A and injectable dexamethasone and subsequently underwent functional evaluation by optomotor response testing and electroretinography (ERG) at multiple intervals from P45 to P180.
Results:
Immunosuppressed RCS animals demonstrated poorer performance on functional tests than age-matched untreated rats during the earlier stages of degeneration, including significantly lower spatial acuities on optomotor threshold testing and significantly lower b-wave amplitudes on scotopic and photopic ERGs. Retinal imaging documented the progression of degenerative changes in the RCS fundus and histologic evaluation of the RCS retina confirmed progressive thinning of the outer nuclear layer.
Conclusions:
A standard regimen of cyclosporine A plus dexamethasone, administered to RCS rats, results in demonstrable systemic side effects and depressed scores on behavioral and electrophysiological testing at time points before P90. The source of the functional impairment was not identified. This finding has implications for the interpretation of data generated using this commonly used translational model.
Insights
Immunosuppression in Royal College of Surgeons (RCS) rats impairs visual function and test performance. This impacts data interpretation in translational studies using this common animal model.
Area of Science:
- Ophthalmology
- Neuroscience
- Pharmacology
Background:
- Immunosuppression is vital for xenograft survival in translational research.
- Potential side effects of immunosuppressive regimens are often overlooked.
- The Royal College of Surgeons (RCS) rat is a model for retinal degeneration.
Purpose of the Study:
- To evaluate the impact of immunosuppression on visual function in RCS rats.
- To assess functional changes in immunosuppressed RCS rats compared to controls.
- To understand implications for translational research using RCS rats.
Main Methods:
- RCS rats and Long Evans controls were used.
- Animals received either no treatment or systemic immunosuppression (cyclosporine A and dexamethasone).
- Functional evaluation included optomotor response testing and electroretinography (ERG) from P45 to P180.
Main Results:
- Immunosuppressed RCS rats showed poorer functional test performance before P90.
- Lower spatial acuities and reduced ERG b-wave amplitudes were observed.
- Retinal imaging and histology confirmed progressive retinal degeneration.
Conclusions:
- Standard immunosuppression regimens (cyclosporine A plus dexamethasone) cause systemic side effects in RCS rats.
- These side effects depress behavioral and electrophysiological test scores.
- Findings necessitate careful consideration when interpreting data from immunosuppressed RCS rat models.
