A life’s work in the inner ear
Raúl Hinojosa Prieto was born June 18, 1928, in Tampico Tamaulipas, México. He studied Medicine at the National Autonomous University of México and later specialized in Pathology. Raúl Hinojosa Prieto left Mexico to secure a better future for himself and his family in the United States, like many other Mexican academics, a brain drain caused by the relative lack of resources for science in his native country. Upon emigrating, Raúl stopped following the Spanish tradition of combining both paternal and maternal family names, and became Raúl Hinojosa.
In 1962, Dr. Hinojosa joined the otolaryngology section of the surgical faculty at the University of Chicago as an Assistant Professor. He was promoted to Research Associate Professor in 1968 and to Associate Professor in 1988, and retired with emeritus status in 1998. Dr. Hinojosa was a respected teacher of generations of medical students and residents, in temporal bone pathology, hearing loss, cochlear implants and the research applications of electron microscopy. His pioneering investigations of the inner ear are summarized in 86 research papers and 11 book chapters. As elaborated on below, Dr. Hinojosa made seminal contributions to our understanding of the histopathological changes in the inner ear wrought by disease, aging, and ototoxic insults. He also studied normal and comparative structure and development of the inner ear, contributing some of the finest electron microscopic preparations ever done (see, for examples, Hunter-Duvar and Hinojosa, 1984).
Dr. Hinojosa’s work in the inner ear can be traced to the 1960’s. With Dr. Rodriguez-Echandia, he described the complex structure and large mitochondria of the stria vascularis, required for ion transport and the generation of the endocochlear potential (Hinojosa and Rodriguez-Echandia, 1966; see also Hinojosa, 1971, 1972; Fernández and Hinojosa 1974). Much of his subsequent work described inner ear histopathology. His studies were influential in establishing idiopathic perilymphatic fistula as a separate inner ear disease (Kohut et al., 1995, 1996). Further studies with Dr. Robert Kohut were some of the first to thoroughly examine temporal bones from individuals who suffered a labyrinthine arterial vascular accident, revealing damage to the vestibular nuclei, facial and trigeminal nerves, restiform body, and middle cerebellar peduncle, as well as damage to the labyrinth, including loss of cochlear and vestibular sensory epithelia and the vestibular nerve and ganglion (Hinojosa and Kohut, 1990). He studied inner ear damage in Reye`s syndrome (Hinojosa and Lindsay, 1977) and other rare diseases. In patients with Benign Paroxysmal Positional Vertigo (BPPV), Hinojosa and colleagues demonstrated a statistically significant association between symptoms and the presence of particles within the posterior semicircular canal, even recovering one of the particles (Welling et al., 1997). Nelson and Hinojosa (2006) investigated age-related histopathological changes in the cochlea, showing that individuals with presbycusis have degeneration of the stria vascularis, spiral ganglion cells, and inner and outer hair cells that correlates with the severity of hearing loss.
Dr. Hinojosa and colleagues significantly contributed to our knowledge of inner ear damage from the toxic medicines, aminoglycosides and cisplatin (Thomas et al., 1992). They showed that cisplatin induced loss of inner and outer hair cells, degeneration of the stria vascularis, and a significant decrease in spiral ganglion cells, predominantly in the cochlear apex (Hinojosa et al., 1995). Retrospective studies of aminoglycoside ototoxicity in human temporal bones showed reduction of both hair cell and spiral ganglion cell populations. Unexpectedly, spiral ganglion cells may be reduced in parts of the cochlea with normal-appearing hair cells, implying that aminoglycoside antibiotics injure spiral ganglion cells directly and that hearing loss can result from degeneration of either hair cells or afferent neurons (Hinojosa et al., 2001; Nelson and Hinojosa 2005, 2006).
Dr. Hinojosa significantly expanded the University of Chicago’s temporal bone collection, started by Dr. John Lindsay. Analysis of these temporal bones has yielded several key insights. For example, in a patient with connexin 26-related deafness, a common cause of non-syndromic deafness, the spiral ganglion was observed to be preserved, suggesting the feasibility of cochlear implantation in this important patient population (Jun et al., 2000). In cochlear mitochondrial DNA (mtDNA) isolated from minute quantities of human archival temporal bone tissue, Seidman et al. (1996) found the 4977-bp mtDNA deletion in patients with presbycusis, demonstrating that specific mtDNA defects from a single cochlea can be correlated with pathological processes. Late in his career, Dr. Hinojosa worked to develop methods to expand the range of studies feasible with archival temporal bones to include proteomic analysis and RT-PCR in laser-microdissected spiral ganglia (Markaryan 2008a-c, 2010a-b, 2011).
In addition to questions of clinical relevance, Raúl Hinojosa was interested in the evolution, comparative anatomy, and development of inner ear structures. He conducted ultrastructural analyses of afferent synapses in the inner ears of such diverse species as goldfish (Hinojosa, 1973), axolotl (Hinojosa et al., 1984) and echidna (Griffiths, 2012). He showed the role of autophagy in the development of the organ of Corti (Hinojosa, 1977). In the chick vestibular inner ear, Meza and Hinojosa (1987) described ontogenetic changes in neurotransmitter synthetic enzymes.
This brief summary of Raúl Hinojosa’s scientific contributions constitutes a small tribute to the merits of a scientific life devoted to study of the fine structure and pathology of the inner ear. Raúl Hinojosa’s fine personal qualities were essential to his academic and human development; he was one of the most peaceful and polite persons I have ever met. His family and friends should be proud of him and his intellectual legacy. (See http://www.uchospitals.edu/news/2015/20150728-hinojosa.html.)
This essay is intended as a celebration of a well-lived life by a distinguished medical academician and colleague, and a reminder that our deep understanding of auditory and vestibular processes depends on the contributions of those who came before, to whom we pay tribute and respect for the scientific edifice that we inhabit.
Enrique Soto, PhD
Meritorious Autonomous University of Puebla
Instituto de Fisiología
Fernández C, Hinojosa R. (1974) Postnatal development of endocochlear potential and stria vascularis in the cat. Acta Otolaryngol. 78 (3-4):173-186.
Griffiths M. (2012) The Biology of the Monotremes. Elsevier.
Hinojosa R, Kohut RI. (1990) Clinical diagnosis of anterior inferior cerebellar artery thrombosis. Autopsy and temporal bone histopathologic study. Ann Otol Rhinol Laryngol. 99(4 Pt 1):261-272.
Hinojosa R, Lerner SA. (1987) Cochlear neural degeneration without hair cell loss in two patients with aminoglycoside ototoxicity. J Infect Dis. 156(3):449-455.
Hinojosa R, Lindsay JR. (1977) Inner ear degeneration in Reye's syndrome. Arch Otolaryngol. 103(11):634-640.
Hinojosa R, Nelson EG, Lerner SA, Redleaf MI, Schramm DR. (2001) Aminoglycoside ototoxicity: a human temporal bone study. Laryngoscope. 111(10):1797-1805
Hinojosa R, Nelson EG. (2011) Cochlear nucleus neuron analysis in individuals with presbycusis. Laryngoscope. 121(12):2641-2648.
Hinojosa R, Riggs LC, Strauss M, Matz GJ. (1995) Temporal bone histopathology of cisplatin ototoxicity. Am J Otol. 16(6):731-740.
Hinojosa R, Rodriguez-Echandia EL. (1966) The fine structure of the stria vascularis of the cat inner ear. Am J Anat. 118(2):631-663
Hinojosa R. (1977) A note on development of Corti's organ. Acta Otolaryngol. 84(3-4):238-251
Hinojosa R. (1972) Electron microscope studies of the stria vascularis and spiral ligament after ferritin injection. Acta Otolaryngol. 74(1):1-14.
Hinojosa R. (1971) Transport of ferritin across Reissner's membrane. Acta Otolaryngol Suppl. 292:1-27.
Hinojosa R, Soto E, Vega R y Budelli R. (1984) Análisis de la estructura y polarización funcional del oído interno del axolotl, usando microscopía electrónica de barrido. XXVII Congreso Nacional de Ciencias Fisiológicas. Resúmenes pag. 138
Hunter-Duvar IM, Hinojosa R. (1984) Vestibule: sensory epithelia. In: Friedmann I, Ballantyne J, editors. Ultrastructural atlas of the inner ear. London: Butterworths. p 211–244.
Jun AI, McGuirt WT, Hinojosa R, Green GE, Fischel-Ghodsian N, Smith RJ. (2000) Temporal bone histopathology in connexin 26-related hearing loss. Laryngoscope. 110(2 Pt 1):269-275
Kohut RI, Hinojosa R, Howard G, Ryu JH. (1995) The accuracy of the clinical diagnosis (predictability) of patencies of the labyrinth capsule (perilymphatic fistulas): a clinical histopathologic study with statistical evaluations. Acta Otolaryngol Suppl.520 Pt 1:235-237.
Kohut RI, Hinojosa R, Ryu JH. (1996) Update on idiopathic perilymphatic fistulas. Otolaryngol Clin North Am. 29(2):343-52.
Kohut RI, Hinojosa R, Thompson JN, Ryu JH. (1995) Idiopathic perilymphatic fistulas. A temporal bone histopathologic study with clinical, surgical, and histopathologic correlations. Arch Otolaryngol Head Neck Surg. 121(4):412-420.
Markaryan A, Nelson EG, Helseth LD, Hinojosa R. (2010) Proteomic analysis of formalin-fixed celloidin-embedded whole cochlear and laser microdissected spiral ganglion tissues. Acta Otolaryngol. 130(9):984-989.
Markaryan A, Nelson EG, Hinojosa R. (2008) Detection of mitochondrial DNA deletions in the cochlea and its structural elements from archival human temporal bone tissue. Mutat Res. 640(1-2):38-45.
Markaryan A, Nelson EG, Hinojosa R. (2011) Duplex real-time PCR assay for quantifying mitochondrial DNA deletions in laser microdissected single spiral ganglion cells. Methods Mol Biol. 755:315-326.
Markaryan A, Nelson EG, Hinojosa R. (2010) Major arc mitochondrial DNA deletions in cytochrome c oxidase-deficient human cochlear spiral ganglion cells. Acta Otolaryngol. 130(7):780-787.
Markaryan A, Nelson EG, Tretiakova M, Hinojosa R. (2008) Technical report: laser microdissection of cochlear structures from celloidin embedded human temporal bone tissues and detection of the mitochondrial DNA common deletion using real time PCR. Hear Res. 244(1-2):1-6.
Markaryan A, Nelson EG, Tretiakova M, Hinojosa R. (2008) Technical report: immunofluorescence and TUNEL staining of celloidin embedded human temporal bone tissues. Hear Res.241(1-2):1-6.
Meza G, Hinojosa R. (1987) Ontogenetic approach to cellular localization of neurotransmitters in the chick vestibule. Hear Res.28(1):73-85.
Nelson EG, Hinojosa R. (2005) Age-related histopathologic changes in the human cochlea. Otolaryngol Head Neck Surg. 133(5):817.
Nelson EG, Hinojosa R. (2006) Presbycusis: a human temporal bone study of individuals with downward sloping audiometric patterns of hearing loss and review of the literature. Laryngoscope. 116(9 Pt 3 Suppl 112):1-12. Review.
Seidman MD, Bai U, Khan MJ, Murphy MJ, Quirk WS, Castora FL, Hinojosa R. (1996) Association of mitochondrial DNA deletions and cochlear pathology: a molecular biologic tool. Laryngoscope. 106(6):777-783.
Thomas J, Marion MS, Hinojosa R. (1992) Neomycin ototoxicity. Am J Otolaryngol. 13(1):54-55.
Welling DB, Parnes LS, O'Brien B, Bakaletz LO, Brackmann DE, Hinojosa R. (1997) Particulate matter in the posterior semicircular canal. Laryngoscope. 107(1): 90-94.