Retinal morphological and functional changes in an animal model of retinitis pigmentosa

Bin Lu, Catherine Morgans, Sergey Girman, Raymond Lund, Shaomei Wang

    Research output: Contribution to journalArticle

    9 Citations (Scopus)

    Abstract

    Abstract The P23H-1 transgenic rat carries a mutated mouse opsin gene, in addition to endogenous opsin genes, and undergoes progressive photoreceptor loss that is generally characteristic of human autosomal dominant retinitis pigmentosa (RP). Here, we examined morphological changes correlated with visual function that is comparable to clinical application in the pigmented P23H-1 rat retina as photoreceptor degeneration progressed. We found that rod function was compromised as early as postnatal day 28 and was a good indicator for tracking retinal degeneration. Cone function was normal and did not change until the thickness of the photoreceptor layer was reduced by 75%. Similar to the threshold versus intensity curves used to evaluate vision of RP patients, light-adaptation curves showed that cone thresholds depended on the number of remaining functioning cones, but not on its length of outer segments (OS). By 1 year of age, both rod and cone functions were significantly compromised. Correlating with early abnormal rod function, rods and related secondary neurons also underwent progressive degeneration, including shortening of inner and OS of photoreceptors, loss of rod bipolar and horizontal cell dendrites, thickening of the outer Müller cell processes, and reduced density of pre- and postsynaptic markers. Similar early morphological modifications were also observed in cones and their related secondary neurons. However, cone function was maintained at nearly normal level for a long period. The dramatic loss of rods at late stage of degeneration may contribute to the dysfunction of cones. Attention has to be focused on preserving cone function and identifying factors that damage cones when therapeutic regimes are applied to treat retinal degeneration. As such, these findings provide a foundation for future studies involving treatments to counter photoreceptor loss.

    Original languageEnglish (US)
    Pages (from-to)77-89
    Number of pages13
    JournalVisual Neuroscience
    Volume30
    Issue number3
    DOIs
    StatePublished - May 2013

    Fingerprint

    Opsins
    Retinal Degeneration
    Retinitis Pigmentosa
    Animal Models
    Ocular Adaptation
    Transgenic Rats
    Retinal Rod Photoreceptor Cells
    Post-Synaptic Density
    Neurons
    Vertebrate Photoreceptor Cells
    Dendrites
    Genes
    Retina
    Therapeutics

    Keywords

    • P23H mutation
    • Retinal degeneration
    • Retinitis pigmentosa
    • Rod and cone
    • Visual function

    ASJC Scopus subject areas

    • Sensory Systems
    • Physiology
    • Medicine(all)

    Cite this

    Retinal morphological and functional changes in an animal model of retinitis pigmentosa. / Lu, Bin; Morgans, Catherine; Girman, Sergey; Lund, Raymond; Wang, Shaomei.

    In: Visual Neuroscience, Vol. 30, No. 3, 05.2013, p. 77-89.

    Research output: Contribution to journalArticle

    Lu, Bin ; Morgans, Catherine ; Girman, Sergey ; Lund, Raymond ; Wang, Shaomei. / Retinal morphological and functional changes in an animal model of retinitis pigmentosa. In: Visual Neuroscience. 2013 ; Vol. 30, No. 3. pp. 77-89.
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