Treatment with 216A-targeted ASOs to neonate mice corrected protein expression with an improvement in harmonin localization in the hair cells and photoreceptors rescued vestibular and hearing function, and demonstrated a small improvement in visual function. Cell-free and cellular assays also demonstrated that ASOs targeted to the Ush1c.238dupC mutation result in in-frame skipping of exon 3. Visual function was evaluated by electroretinogram (ERG) analyses and optical coherence tomography (OCT) imaging was used to examine ocular structures.ĪSOs effectively corrected splicing of 216A RNA in an Usher patient cell line, and in the cochleae and retinas of 216AA mice when delivered systemically or locally. Hearing and vestibular function were evaluated by auditory-evoked brain stem response (ABR) and open-field chamber analysis, respectively. Immunofluorescence was used to analyze Harmonin expression and ASO localization. Correction of splicing was evaluated by RT-PCR and western blot.

This mouse model provides an opportunity to test the feasibility of correcting the disease-associated genetic defect using antisense oligonucleotides (ASOs).Īntisense oligonucleotides (ASOs) were used to target Ush1c mutations in vitro and in vivo by systemic or local injection. 216AA mice exhibit circling behavior indicative of severe vestibular dysfunction and deafness, have retinal dysfunction by 1 month of age and begin to lose photoreceptors after 6 months of age. We created a mouse model for Usher 1C by knocking in the 216A mutation. The 216G>A (216A) mutation in USH1C creates a cryptic splice site that is used preferentially over the correct site and results in a truncated harmonin protein. Type 1 Usher (Usher 1) is characterized by profound hearing impairment and vestibular dysfunction at birth, and the development of retinitis pigmentosa (RP) in early adolescence. Post Menopause is one of the most dynamic phases of a woman's life let's not judge it before it's begun.Usher syndrome (Usher) is the leading genetic cause of combined deafness and blindness. Let’s not shy away or hedge our bets, let’s encourage women to stand tall as they declare this phase in their life. Menopausal and post-Menopausal women are a burgeoning market. It is about time that brands spoke directly to us, representing us with images of women of our own age. We have to start to recognise at the very least, that as women in our 50s we are still beautiful, dynamic and a force to be reckoned with. This is no comfort to the one in every 100 women who experience theirs before the age of 40. Our societal perceptions are such that Menopause is seen as an older or mature woman’s affliction. Many women have told me that either they or their colleague have, since declaring that they were Menopausal, have felt that their career has stalled.

Women still find themselves the subject of inappropriate humour and outdated, age-based judgement and ridicule.

Women are often uncomfortable declaring that they are Menopausal at work and in their personal lives, for fear of being branded old or past it.

Why does this bother me so much? Let me tell you. Whilst I appreciate you don’t want to insult women of my age by using a model in her thirties (or younger) – many high street brands touting for our business please take note – do not swing the other way and use a woman much older than us, simply to ensure society can confidently age bracket the product and to feel comfortable in it’s historic assumptions surrounding the Menopause. The average age of post-Menopause here and in the US. The model used, whilst stunningly beautiful is considerably older than a 52 year old. But, I am sorry to say, Prai, you have made the classic mistake in your face cream for post-Menopausal women ad! I love Prai, I have used their neck cream since finding it in the M&S advent calendar, which I also love. I recently saw an advert for beauty brand Prai.

Kate usher age