A WHRN mutation impacts ocular morphology in rhesus macaques.

BACKGROUND

Rhesus macaques are increasingly used to model inherited sensory disorders, yet the phenotypic impact of naturally occurring variants in primate colonies often remains undefined.

METHODS

We identified five rhesus macaques homozygous for a missense variant in WHRN (p.Val495Met in exon 7), which encodes whirlin and is implicated in human Usher syndrome type 2D, and compared them with five age and sex matched wild-type controls (WHRN homozygotes: mean age 9.4 ± 1.8 years; controls: mean age 8.6 ± 1.1 years) using standardized ocular and auditory phenotyping, including comprehensive ophthalmic examination, A-scan ocular biometry, intraocular pressure measurement, cycloplegic refraction, macular optical coherence tomography with retinal layer thickness quantification, full-field electroretinography, and brainstem auditory evoked response testing.

RESULTS

WHRN homozygotes showed a consistent shift in ocular component dimensions, with significantly reduced lens thickness, while refractive error remained centered near emmetropia. By contrast, fundus examination and macular optical coherence tomography showed preserved retinal morphology, electroretinography waveforms were comparable between groups, and brainstem auditory evoked responses did not show evidence of overt hearing impairment under the recording conditions used.

CONCLUSION

These findings define a subtle ocular biometry phenotype associated with WHRN p. Val495Met homozygosity in rhesus macaques, while retinal structure and function were preserved at the time of testing; more comprehensive auditory phenotyping across frequencies and thresholds will be needed to assess whether subtle, frequency specific hearing deficits consistent with an atypical Usher presentation are present.